HPN January 2024 by IPN Communications LTD

HOSPITAL PROFESSIONAL NEWS IRELAND

HPN January 2024 Issue 116 HOSPITALPROFESSIONALNEWS.IE

Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: Hospital Pharmacy Technicians launch Campaign Page 4 REPORT: Preventing Intentional Drug Overdose Page 14 RESPIRATORY FOCUS: Optimising COPD Management Page 18 HONOURS: Hospital Professional Honours Page 35

Legal Category: Product subject to prescription which may be renewed (B). Marketing Authorisation Number: EU/1/12/795/002; EU/1/12/795/007. Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15. Tel: +353 1 609 71 00. FORXIGA is a trademark of the AstraZeneca group of companies.

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This Publication is for Healthcare Professionals Only

CPD: Chronic Kidney Disease Page 37 FEATURE: Current Management of Motor Neurone Disease Page 42 STUDY: Characterising Kidney Disease Page 45

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AbbVie® is a registered trademark of AbbVie Inc. RINVOQ® and its design are registered trademarks of AbbVie Inc. REFERENCES: 1. RINVOQ® summary of product characteristics, available at www.medicines.ie. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. Legal Classification: POM(S1A). IE-RNQG-230034 | August 2023

January Issue Issue116

Contents

Foreword

St Vincent’s Cancer UCD Centre unveiled P5

Editor

Ireland continues to wait for access to medicines P6

As Hospital Professional News was going to press, the Minister for Health Stephen Donnelly announced ¤20 million in funding for new medicines in 2024.

New research on Antibiotic Resistance P8

This funding is in addition to the record almost ¤3 billion being spent this year on medicines. This represents nearly ¤1 in every ¤8 of public funding being spent on health. This unprecedented level of investment in our health services will support access for patients to the latest range of medicines.

New Leadership Team at Medicines for Ireland P12

Meanwhile, at an Oireachtas briefing session held last month TDs and Senators heard of the human impact of delayed access to new, innovative medicines and the consequences for patients of no dedicated funding.

Preventing intentional overdose with Paracetamol P14 Priorities outlined for Diabetes P48

Multidisciplinary approaches to Ovarian Cancer P50 National Skin Cancer Service being ‘blocked’ P53

Irish patients continue to fall behind those in other European countries. As per the IPHA Agreement, Ireland is referenced against 14 basket countries, and we have identified medicines that are currently available in all or in most of these countries but not here for Irish patients. These are medicines which can improve the health outcomes of patients and make a significant difference to their quality of life,” said IPHA Chief Executive Oliver O’Connor.

REGULARS

Respiratory Focus: COPD P18

Respiratory Focus: Robotic Assisted Thoracic Surgery P22

You can read more about this on page 6.

CPD: Chronic Kidney Disease P37 Clinical R&D: P60 Hospital Professional News is a publication for Hospital Professionals and Professional educational bodies only. All rights reserved by Hospital Professional News. All material published in Hospital Professional News is copyright and no part of this magazine may be reproduced, stored in a retrieval system or transmitted in any form without written permission. IPN Communications Ltd have taken every care in compiling the magazine to ensure that it is correct at the time of going to press, however the publishers assume no responsibility for any effects from omissions or errors.

SALES EXECUTIVE Avril Boyd avril@hospitalprofessionalnews.ie SALES & TRAINING MANAGER Sibongile Mude s.mude@hospitalprofessionalnews.ie CONTRIBUTORS

GROUP DIRECTOR Natalie Maginnis n-maginnis@btconnect.com

Michelle O’Driscoll Dr Dhiviya Ganesan Dr Sinéad Walsh Dr Laura Staunton Ms Rebecca Weedle Mr Ronan Ryan Mr Vincent Young Mr Gerard J. Fitzmaurice Ruth Morrow Philip Watt Austin Stack Dr Colm Rowen Professor Orla Hardiman Dr Grace O’Malley

EDITOR Kelly Jo Eastwood

DESIGN DIRECTOR Ian Stoddart Design

EDITORIAL danielle@hospitalprofessionalnews.ie

HOSPITALPROFESSIONALNEWS.IE

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562

ACCOUNTS Fiona Bothwell cs.ipn@btconnect.com

The Irish Pharmaceutical Healthcare Association (IPHA) presented data describing medicines which were planned for 2024 that may not now progress due to lack of new development funding. These same medicines are already available in many other European countries, including Northern Ireland, highlighting the inadequacies of the current system for Irish patients.

@HospitalProNews HospitalProfessionalNews

Staying on the focus of medicines, on page 13 the European Association of Hospital Pharmacists (EAHP) has welcomed the Communication on medicine shortages adopted by the European Commission (EC), as well as The Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) Toolkit on recommendations on tackling shortages of medicinal products and MSSG Solidarity Mechanism adopted by the EMA. In other news, the National Hospital Pharmacy Technicians Association of Ireland recently launched their Statutory Campaign for Hospital Pharmacy Technicians at Forsa Headquarters. ’30 Years without Review’ seeks statutory regulation for hospital pharmacy technicians in Ireland. Our Special Focus for January is on Respiratory issues and we once again have some excellent clinically contributed content, including Dr Dhiviya Ganesan and Dr Sinéad Walsh discussing the integrated care paradigm in optimising COPD management. I hope you enjoy the issue.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

News

Hospital Pharmacy Technician launch Campaign NAHPT Committee members including Rebekah Corrigan, Vice President, Leonor O’Connor, President Laura Lyons and Gillian Cawley

The National Hospital Pharmacy Technicians Association of Ireland recently launched their Statutory Campaign for Hospital Pharmacy Technicians at Forsa Headquarters. ’30 Years without Review’ seeks statutory regulation for hospital pharmacy technicians in Ireland. The campaign explores the critical issue of statutory regulation for Hospital Pharmacy Technicians, and its implications in the Republic of Ireland. Despite their pivotal role, the lack of an official definition and regulatory framework for Hospital Pharmacy Technicians in the Republic of Ireland is glaring. While NAHPT and Hospital Pharmacy

Staff collaborate with select educational institutions to shape and assess Pharmacy Technician programmes, the absence of statutory regulation means that there is no standardised benchmark for education and training across all institutions in the country. This gap leaves the profession without a protected title, co-ordinated professional development, consistency in the quality of care, and career progression prospects.

urgently propose legislative amendments to the Pharmacy Act of 2007 to encompass Hospital Pharmacy Technicians within the PSI's regulatory purview, mirroring the regulation of Pharmacists. Such alignment under a common code of ethics would solidify trust among employers and patients in the quality of care provided by Hospital Pharmacy Technicians.

The impending healthcare changes under Sláintecare reform, coupled with the diverse demands of an aging population, and the restructuring of the Hospital Pharmacist role, necessitates a re-evaluation of the Hospital Pharmacy Technician role. Astonishingly, the career structure for this role has remained largely unchanged since the creation of the senior grade in 1994, a lapse of nearly three decades that compromises both the skilled professionals operating in this capacity and the service users relying on their expertise.”

Fórsa national secretary Linda Kelly with Leonor O’Connor, NAHPT Committee Member

The campaign states, “As advocates and union representatives for Hospital Pharmacy Technicians, we assert that the Minister of Health must

University of Galway joins Translational Medicine Alliance University of Galway has joined a new, cross-border higher education alliance to strengthen partnerships between scientists and clinicians and foster impactful research that translates from the lab to patient care. Translational Medicine Alliance Ireland (TMAI) has been established with 10 universities and technological universities on the island of Ireland. The alliance of academics and researchers will have a focus on the development of new diagnostics, therapies, and medical interventions. Collaboration in translational medicine serves as a catalyst for

transforming scientific discoveries into practical applications that directly benefit patients and society. Translational Medicine Alliance Ireland (TMAI) will enable the pooling of higher education resources, knowledge and skills. It will also offer a platform for researchers and institutions engaged in translational medicine to generate novel ideas and develop innovative therapies or diagnostics more efficiently, enhancing the impact and success of their translational research and elevating the visibility and reputation of the biomedical research community on the global stage.

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Professor Aideen Long, Director, Trinity Translational Medicine Institute (TTMI), said, “The establishment of TMAI is a testament to the belief that collectively forging connections, building bridges, and creating a network of translational research institutes will achieve far more than any one of us could envision alone - in terms of pushing new boundaries, breaking barriers, and realising impactful clinical research outcomes that will ultimately benefit patients." Dr Pilib Ó Broin, Assistant Professor in Translational Bioinformatics, University of

Galway, added, "We are delighted to join TMAI and firmly believe that leveraging complementary expertise across our partner institutions is key to accelerating innovation in translational research at a national level. Galway's translational research excellence and infrastructure, including our newly-established research institutes in health discovery and innovation and clinical trials, will greatly enhance the capacity of this new alliance and we look forward to work with our partners in creating meaningful benefit for patients and strengthening Ireland's international reputation in this area."

News

Bed Shortages to Top 3,000 A senior researcher with the Economic and Social Research Institute (ESRI) says the Irish health system is currently experiencing a situation where it is unable to keep up with the population’s demand for care. Speaking in a New Video as part of the Irish Hospital Consultants Association’s (IHCA) Care Can’t Wait campaign, the ESRI’s Dr Brendan Walsh said there is currently a 1,000-bed deficit across public hospitals with an additional 300 extra beds required per annum on top of this figure. This comes at a time when public hospitals are unlikely to be able to provide care to a staggering

73,900 additional people who are on waiting lists before the end of the year, to achieve the Government’s reduction target for 2023.

off, because demand for care is significantly increasing and hospital capacity is insufficient.

an additional 300 beds will be required annually.

Dr Brendan Walsh says the inability of public hospitals to meet this growing demand is due to a lack of planning for sufficient hospital capacity going back several years, along with other issues associated with Covid.

In the new video, Dr Walsh describes the Irish health service as a ‘hostage to fortune’. He says due to people living longer, the demand for healthcare has increased but capacity, workforce and health system changes have not been able to keep up:

“We have seen quite a lot of investment in recent years when it comes to beds, however we’re starting from a very low base and the level of investment has slowed down quite a bit. We are now entering a territory where we’re going to have issues regarding strains in the hospital sector and bed deficits for years to come.

Latest National Treatment Purchase Fund (NTPF) figures show that 883,300 people were on some form of hospital waiting list at the end of October. This indicates that more patients are being added to waiting lists than are being taken

“We have released a research paper where we estimated that the potential deficit within the public hospital system regarding inpatient beds is about 1,000 in the system and based upon continued changes in our demographics

“We must act quickly and move toward community care where it’s appropriate, but we must also understand that there are deficits in our hospital system and try to fill those deficits as quickly as possible.”

Unveiling of St Vincent’s Cancer Centre St. Vincent's Healthcare Group and UCD School Of Medicine has proudly unveiled the St. Vincent’s UCD Cancer Centre. At the official launch event in the Kevin Barry Gallery, Charles Institute, UCD, distinguished speakers including UCD President, Professor Orla Feely, Professor Michael Keane, Professor Risteard O'Laoide, Dr David Fennelly, and Professor William Gallagher shared insights into this ground-breaking initiative. St. Vincent’s UCD Cancer Centre is a collaborative endeavour uniting cutting-edge expertise in highly specialised cancer care and comprehensive cancer research. This joint initiative,

involving the St. Vincent’s Healthcare Group (comprising St. Vincent’s University Hospital and St. Vincent’s Private Hospital) and University College Dublin, is dedicated to setting new standards in cancer treatment and research. The St. Vincent’s UCD Cancer Centre aspires to be at the forefront of cancer service provision in Ireland, ensuring that each patient can access safe, compassionate, and high-quality care when needed. Through high-quality, integrated care, advanced clinical research, and personalised diagnosis and treatment, we are dedicated to delivering the best cancer care for our patients.

UCD President, Professor Orla Feely, Professor Michael Keane, Professor Risteard O'Laoide, Dr David Fennelly, and Professor William Gallagher shared insights into this ground-breaking initiative

Professor Michael Keane, Dean/ Head of School of Medicine, UCD

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

News

Delayed Access to Medicines – Ireland continues to Wait Senator Tim Lombard, Jim McGrath, Director of Commercial Policy at the IPHA; Roisin Molloy, who is recovered from breast cancer but also a former oncology nurse and current General Manager of Merck Serono; and Dr Grainne O’Kane, Medical Oncologist at St. James’ Hospital and Oliver O’Connor, CEO, IPHA

Irish patients may not have the time to wait while these savings are found. It is essential that finding these efficiency savings is prioritised in the absence of dedicated funding. At an Oireachtas briefing session held last month TDs and Senators heard of the human impact of delayed access to new, innovative medicines and the consequences for patients of no dedicated funding. The Irish Pharmaceutical Healthcare Association (IPHA) presented data describing medicines which were planned for 2024 that may not now progress due to lack of new development funding. These same medicines

are already available in many other European countries, including Northern Ireland, highlighting the inadequacies of the current system for Irish patients. Budget 2024 runs the risk of even longer waiting times for patients by potentially interrupting the flow of new medicines from January next year. While a commitment has been made by the government to find funding through existing spend which will be reinvested in new medicines,

Health Literacy Digital Badge The School of Pharmacy, University College Cork (UCC) are delighted to launch a new Digital Badge, “An Introduction to Health Literacy for Health and Social Care Professionals” which is now open for registration. The course, designed and delivered by Professor Laura J Sahm and Dr Michelle O’Driscoll in collaboration with the National Adult Literacy Agency, will begin on 8 January 2024, Monday. It is open to all health and social care professionals, or students of such professions, who are currently or will in the future engage with patients experiencing health literacy challenges, and who wish to optimise their care. The course runs online over ten weeks and is FREE to the first 20 external registrants. An administration fee of ¤12 will apply to external applicants thereafter. To register, please complete the registration form at ucc.ie

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Across all health spending new medicines expenditure is probably the most robustly assessed and budget impact medicines go through a strict evaluation process to determine if they will improve efficiency and standards of care before being made directly available to Irish patients. Acknowledging the importance of imposing a strict funding assessment, the process does however require between 20 and 30 steps before a medicine is approved, taking on average, over 1,000 days from the start of the NCPE assessment to reimbursement.

Oireachtas members were also presented with the result from a recent Ipsos poll conducted on behalf of IPHA which found that: • Four in five Irish people believe that delays exist in public access to new medicines in Ireland. • Compared to our European counterparts, over half believe that access to new medicines is later in Ireland. “The availability of medicines in the provision of healthcare, is a crucial and integral part of ensuring universal health coverage which is essential for a functioning healthcare system. Medicines are key to healthy aging and, given the demographic trends of the Irish population, timely access to medical innovation needs to be a priority. “However, Irish patients continue to fall behind those in other European countries. As per the IPHA Agreement, Ireland is referenced against 14 basket countries, and we have identified medicines that are currently available in all or in most of these countries but not here for Irish patients. These are medicines which can improve the health outcomes of patients and make a significant difference to their quality of life. “To align Ireland with peer countries who adopt medicines faster, we need a continuous and a faster flow of new medicines which will raise the standards of care and health outcomes for Irish patients.” said Oliver O’Connor, Chief Executive, IPHA.

News

SFI Award for Professor Kerrigan Professor Steve Kerrigan from the School of Pharmacy and Biomolecular Sciences at RCSI University of Medicine and Health Sciences has been named winner of the Science Foundation Ireland (SFI) Commercialisation Award 2023. The award was announced at the 2023 Research Summit, a joint summit hosted by SFI and the Irish Research Council (IRC). The SFI Commercialisation Award recognises an entrepreneurial or innovation leadership achievement that has resulted in a significant and demonstrable commercial impact. The award celebrates the entrepreneurial motivation, attitude, and skill required in translating publicly funded research to market. The award recognises Professor Kerrigan’s contribution as a founder of Inthelia Therapeutics, an RCSI spin-out clinical-stage pharmaceutical company that aims to develop personalised therapeutic approaches to treat patients with sepsis. Sepsis is the leading cause of death worldwide,

Pictured (l-r) are Professor Fergal O’Brien, RCSI Deputy Vice Chancellor for Research and Innovation; SFI Commercialisation Award 2023 recipient Professor Steve Kerrigan, RCSI School of Pharmacy and Biomolecular Sciences; and Professor Peter Clinch, Chairman of SFI causing over 11 million deaths globally per year. Professor Steve Kerrigan commented: “I am proud and honoured to receive the 2023 SFI Commercialisation Award. Sepsis remains a major global health challenge with high mortality rates and there is currently no drug available to treat the underlying condition. Through RCSI spin-out company Inthelia Therapeutics, I am proud to lead the advancement of an innovative biomarkerguided, host-targeted therapy towards late-stage clinical trials in early sepsis. Building on my research that has advanced the understanding of the molecular mechanisms that leads to sepsis, I hope that the work of Inthelia

will ultimately make a significant impact on the treatment and outcomes for sepsis.” Professor Fergal O’Brien, Deputy Vice Chancellor for Research and Innovation at RCSI, commented: “Congratulations to Professor Steve Kerrigan on his success as winner of the SFI Commercialisation Award 2023. This recognition of his

ground-breaking work through this prestigious national award is a testament to the outstanding translational research at the RCSI School of Pharmacy and Biomolecular Sciences which is being advanced by RCSI spin-out company Inthelia Therapeutics and will potentially benefit the millions of people who are impacted by sepsis annually.”

Private Hospitals Association Conference Unveils EY Research Findings The Private Hospitals Association (PHA) has been told that more must be done to help educate patients in adapting to new technology and innovation that is currently evolving across Irish healthcare. New findings were revealed in a survey conducted in collaboration with EY and were highlighted at the Association’s annual conference held today at Barberstown in Co Kildare. The PHA, in partnership with EY, undertook an in-depth evaluation of technology adoption across Ireland's independent hospitals. Leading healthcare institutions including Blackrock Health, Bon Secours Health System, Charter Medical Private Hospital, Kingsbridge Private Hospital, Mater Private Network, St. Vincent’s Private Hospital, Saint John of God Hospital, and UMPC, contributed to the report. It noted that multiple factors such as rising costs, shifts to home care, equitable access prioritisation, and workforce challenges are all relevant considerations in the context of the digital health transformation. Globally, the key

focus areas include electronic health records, telehealth, differentiated care delivery models, robotics, implants, artificial intelligence, augmented reality, and virtual reality. The EY study found that while Ireland is showcasing world-class innovations in patient treatments, patient experience, and hospital management, a survey of 500 respondents assessing public awareness and readiness, found that just 42% are willing to engage with innovative healthcare solutions despite a 94% awareness level. It also found that telehealth is lagging behind other new technologies in terms of awareness and that men exhibit higher awareness and greater willingness to adopt new technologies, particularly in the case of implants. It concluded that obstacles to adoption persist despite awareness, with age influencing awareness levels. CEO of the Private Hospitals Association, Jim Daly said, “This timely survey underscores the

critical role of digital technologies in the future of healthcare provision, especially with a growing and aging population. Innovation will also be pivotal in addressing emerging gaps in clinical capacity and skills shortages. However there is a clear message coming through which highlights the need to do much more to bring patients on the journey towards change.”

3. Empowering Patients with EHR: Positioning Electronic Health Records (EHR) as empowering for patients - reducing repetition and inefficiency and facilitating seamless transfer within and between healthcare providers such as acute hospital settings, step down, primary care and other healthcare professionals.

The PHA advocates for the following actions to be taken to bridge the gap in patient knowledge and confidence in new healthcare technologies:

4. Future Technological Landscape: Anticipate the use of artificial intelligence for diagnosis, precision robotics in surgery, implant technology for health monitoring, and telehealth for both physical and mental health – and set the scene for change, with patients and their families.

1. Building Patient Knowledge and Confidence: All Stakeholders should collectively enhance patient knowledge and confidence in integrating new technologies into care pathways. 2. Demonstrating Patient Benefits: A specific strategy is needed to demonstrate the added patient benefits arising from technology and innovation, emphasising how such advancements lead to better patient outcomes.

The Private Hospitals Association annual conference serves as a platform to discuss and shape the future of healthcare in Ireland. These findings mark a significant step forward in advancing the integration of transformative technologies into the Irish healthcare landscape.

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

News

Maynooth University research makes progress on tackling antibiotic resistance Rob Elmes and Luke Brennan

Researchers at Maynooth University, working as part of an international team, have created a new molecule that could prove useful in the fight against bacteria showing anti-microbial resistance (AMR).

Pharmaceuticals (SSPC) and the Irish Research Council (IRC), harnessed the principles of supramolecular chemistry, a niche scientific area that explores interactions between molecules, to achieve the breakthrough.

AMR occurs when bacteria, viruses, fungi and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease, severe illness and death. The development of new ways to kill bacteria is an urgent scientific need, as most conventional antibiotics will no longer be effective in 2050 due to the rising levels of AMR.

Most importantly, the study uncovered molecules that are efficient at killing bacteria but whose toxicity to healthy human cells is very low.

The research, supported by Science Foundation Ireland’s Research Centre for

The new research is described in the prestigious journal Chem, to coincide with World AMR Awareness Week which runs from 18-24 November. This global campaign, run by the World Health Organization, aims to raise awareness and understanding of AMR in the hope of reducing the emergence and spread of drugresistant infections.

More than 1.2 million people, and potentially millions more, died in 2019 as a direct result of antibiotic-resistant bacterial infections, according to the most comprehensive estimate to date of the global impact of AMR. This research may pave the way for new approaches to tackle this problem that kills more people annually than HIV/AIDS or malaria. Lead researcher Luke Brennan of MU’s Department of Chemistry said: “We are discovering new molecules and looking at how they bind to anions, which are negatively charged chemicals that are extremely important in the context of the biochemistry of life. We are laying the fundamental foundations that could prove useful in combatting various diseases from cancer to cystic fibrosis.” The work is based on the use of synthetic ion transporters and is the first time that researchers have demonstrated that an influx of salt (sodium and chloride ions) into the bacteria can cause a series of biochemical events that lead to bacterial cell death – even in strains that are resistant to currently available antibiotics

such as methicillin-resistant Staphylococcus aureus (MRSA). Study co-author Dr Rob Elmes of MU’s Kathleen Lonsdale Institute for Human Health Research, says, “This work shows how using our approach, a sort of ‘trojan horse’ that causes an influx of salt into cells, we can effectively kill resistant bacteria in a way that counteracts known methods of bacterial resistance.” Bacteria work hard to maintain a stable concentration of ions inside their cell membranes, and when this delicate balance is disrupted it wreaks havoc on normal cell function and the cells cannot survive. Elmes continued, “These synthetic molecules bind to chloride ions and wrap it up in a ‘fatty blanket’ that allows it to easily dissolve in the bacteria’s membranes, bringing the ions along for the ride and disrupting the normal ionic balance. The work is a great example of foundation knowledge in chemistry fundamentals impacting on unmet needs in human health research.” Prof Kevin Kavanagh, a microbiologist in MU’s Department of Biology commented: “The rising incidence of infections by drug resistant bacteria is a major concern. This work is an example of chemists and biologists working together to pioneer the development of new antimicrobial agents with significant future potential.”

Funding for New Medicines The Minister for Health Stephen Donnelly has announced ¤20 million in funding for new medicines in 2024. This funding is in addition to the record almost ¤3 billion being spent this year on medicines. This represents nearly ¤1 in every ¤8 of public funding being spent on health. This unprecedented level of investment in our health services will support access for patients to the latest range of medicines. Announcing the funding for new medicines, Minister Donnelly said, "This new funding will support patients with cancer, to access

exciting new therapies with the promise of greatly improved health outcomes. Many other clinical areas will benefit from this new funding announcement including chronic kidney disease, drugs used to treat auto-immune conditions as well as inherited and rare disorders." The funding for new drugs will have a positive impact on the lives of thousands of patients. Thanks to the use of new horizon scanning technologies, patients in Ireland will now gain access to new, innovative therapies across a wide range of therapeutic areas. Minister Donnelly added, "While

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

I have continued to ensure new investment year-on-year to support access to new medicines, much more needs to be done by all relevant parties to improve the sustainability of medicines expenditure. I have been clear that in 2024 there must be a focus on drug expenditure to ensure the safe, effective, and cost-effective use of medicines and the identification of new short and long-term opportunities to realise savings and efficiencies. As a starting point, I have asked the HSE to ensure it realises at least ¤10 million in new additional efficiency gains. This money will be re-invested in new drugs and

will ensure that the substantial investment in medicines is maximised to treat even more patients with new therapeutic innovations in the years to come." Going into 2024, the Minister has tasked the Health Service Executive (HSE), the department, and all relevant agencies and stakeholders to place a priority focus on achieving cost savings which can then be considered for additional reinvestment. This will include, for example, the examination of measures to enhance the use of generic and, in particular, biosimilar medicines.

News

Toll of Shortages on Doctors’ Mental Health 93% of doctors in Ireland believe staff shortages present ‘a significant threat’ to patient safety, and nearly 2 in 5 (38%) say the impact on patients is affecting their mental health, according to a survey by the Medical Protection Society (MPS). In the MPS survey of 872 doctors, over a third (36%) say the fear of being sued or investigated due to incidents arising from staff shortages is also having a detrimental impact on their mental health, and two in five (41%) are considering their future in medicine due to the impact of staff shortages on patient safety. The survey results follow a warning from the Irish Medical Organisation (IMO) in September, that public health services face another year of doctor shortages as consultant posts remain

vacant, many younger doctors are emigrating and there are serious difficulties in recruiting GPs. Ireland is already below the OECD average for the number of doctors per head of population. MPS, which protects the professional interests of over 300,000 healthcare professionals around the world, including over 16,000 in Ireland, says urgent action is needed to retain the passionate, committed doctors currently in the workforce, and attract more doctors to Ireland. Dr Rob Hendry, Medical Director at MPS, said, “The fact that most doctors feel the under resourced environments they work in present a significant threat to patient safety, is a sad reflection of the times and is distressing for patients and doctors alike.

“The effect of not being able to provide good care on a doctor’s mental health cannot be overstated, and two in five of the doctors we surveyed say they are reconsidering their career in healthcare because of this. “Many doctors are also worrying about becoming embroiled in medicolegal issues following adverse incidents arising due to staff shortages outside of their control. “When doctors’ mental health is poor it is not only damaging for them but can also jeopardise patient care. The winter period is always challenging, however staff shortages are creating extreme pressure this winter. Furthermore, most doctors who took part in our survey (83%) can’t see staffing levels improving in the foreseeable future.

“One of the many problems with staff shortages - aside from patient safety - is the knock-on effect on the exhaustion and mental health of remaining staff. We need to see urgent steps towards retaining the passionate, committed doctors currently in the workforce but on the verge of quitting, and attracting more doctors to Ireland both in the short and long term. “We encourage healthcare professionals who are struggling, to make use of the mental wellbeing resources available. For example, MPS provides an independent, 24/7 counselling service as a benefit of membership. There is also the Practitioner Health Matters Programme, the IMO’s Doctor Health and Wellbeing hub and the Health in Practice Programme which is run by the Irish College General Practitioners.”

Celebrating 20 years of Scientific Excellence and impact An Tánaiste, Minister for Foreign Affairs and Minister for Defence, Mr. Micheál Martin, T.D. has launched a 20 Years Impact brochure for APC Microbiome Ireland (APC) a world leading SFI Research Centre at a celebration event at The Glucksman Gallery, University College Cork (UCC).

Dr Siobhain O’ Mahony, a researcher at APC Microbiome Ireland and Senior Lecturer in the Department of Anatomy and Neuroscience at University College Cork

Launched in 2003 at UCC, APC was one of the very first microbiome research institutes worldwide and is now one of the largest globally, and has developed into a world-renowned research and scientific leader in the field. The growing economic impact of APC Microbiome Ireland is now calculated at ¤73.7m annually, up from ¤65m five years ago. The research centre supports more than 500 jobs in Ireland each year and returns ¤6.56 to the Irish Economy for every ¤1 invested. APC carries out pioneering microbiome research and has produced more than 3000 peerreviewed scientific publications which has led to advancements in tackling some of the most pressing societal challenges of our time including antimicrobial resistance and the threat of superbugs, the burden of chronic diseases, obesity and malnutrition, mental health, and healthy ageing. The Institute has been particularly successful in collaborating with industry to develop science-based probiotics and other products. With

more than ¤72 million in research funding secured from Industry, APC has attracted foreign direct investment from 11 companies that only have a footprint in Ireland because of APC. The institute has also spun out five companies that now employ 100 people in Cork and its founding SME partner, Cork-based PrecisionBiotics Ltd was acquired by Danish giant Novozymes in 2020. APC also commissioned the first national survey to establish the level of microbiome awareness in the country. The survey found that over one in three respondents are aware of the term ‘microbiome’, with a higher awareness (over 50%) in the 20-29yrs cohort. However, over half of all respondents were familiar with having a gut flora while 85% of respondents are aware of

the term probiotics. Encouragingly, about half of respondents stated they were taking steps to keep their microbiome or gut flora healthy. Almost two thirds of respondents believe that microbiome plays a role in medicine while only 38% believe there is a connection Environmental Sustainability. An encouraging 66% of respondents felt it was important invest in science and research into microbiomes. APC Microbiome Ireland Director Prof Paul Ross says “Over 20 years we are proud to have grown APC Microbiome Ireland into the largest microbiome research centre in the world. We are known for our scientific excellence and the calibre of our researchers which both sets us apart and attracts global stars to work here with us in

Ireland. Our Principal Investigators have received no less than 164 significant distinctions and awards, and we have 13 researchers featured on the 2023 Clarivate’s highly cited Researcher list.” Director General of Science Foundation Ireland, Professor Philip Nolan, commented, “APC is an international leader in microbiome research. In the last ten years, its reputation for scientific excellence has attracted staff and students from 59 countries around the world. APC collaborates with industry partners and scientific peers the world over to mobilise the microbiome science for the good of society. We are pleased to support APC through our SFI Research Centres programme, and to mark this important milestone.”

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

10 News

Cardiac Arrhythmia Symposium

Dr Peter Murray , Dr Steven Williams, Dr Noel Fitzpatrick, Dr Jonathan Lyne, Dr Louisa O’Neill, Dr Matt Wright, Professor Mattias Duytschaever, Dr John Keaney, Professor Mark O’Neill, Dr Daniel O’Hare at Blackrock Clinic Blackrock Health hosted a Cardiac Arrhythmia Symposium on Saturday 18th November at Blackrock Clinic. The event focused on new advances in the treatment of arrhythmias and was a forum to discuss the exchange of knowledge and best practice techniques. World-leading

Professor David Keane, Consultant Cardiologist, speaking at Blackrock Health’s Cardiac Arrhythmia Symposium at Blackrock Clinic

electrophysiologists provided cutting-edge insight into treating cardiac arrhythmias, with a special focus on atrial fibrillation.

Electrophysiology, Guy’s and St Thomas’ Hospital, London, who spoke about new advances in atrial fibrillation.

Speakers on the day included:

• Professor Mattias Duytschaever, Professor in Electrophysiology, University of Ghent & St Jan Hospital Bruges, who discussed radiofrequency ablation in the era of pulsed-field ablation.

• Professor Mark O’Neill, Consultant Cardiologist and Professor of Cardiac

• Dr Matt Wright, Consultant Cardiologist and Electrophysiologist, Guy’s and St Thomas’ Hospital, London, who discussed efficiency in the electrophysiology lab.

Professor Mark O’Neill, Consultant Cardiologist and Professor of Cardiac Electrophysiology speaking at Blackrock Health’s Cardiac Arrhythmia Symposium at Blackrock Clinic

• Dr Steven Williams, Honorary Consultant Cardiologist, University of Edinburgh/NHS Lothia who spoke about the use of artificial intelligence in personalised medicine. Following an introduction from James O'Donoghue, CEO of Blackrock Clinic, the event sessions were chaired by Consultant Cardiologists Dr Louisa O'Neill, Dr Daniel O'Hare and Dr John Keaney, all practicing in Blackrock Health. James O'Donoghue, CEO of Blackrock Clinic, part of Blackrock Health said, "We were honoured to be joined by such eminent clinicians specialising in electrophysiology. The Cardiac Arrhythmia Symposium stands as a pivotal element in the ongoing professional growth and the cultivation of world-class expertise among our esteemed medical practitioners at Blackrock Health. We are confident this knowledgesharing will contribute immensely to the quality of care and outcomes for individuals entrusting us with their cardiac health."

Pharmaceutical Education and Training Key priorities and challenges in pharmaceutical professional education and training systems across 21 selected countries are shared in a new report from the International Pharmaceutical Federation (FIP). The report is one of a series developed under the federation’s Multinational Needs Assessment Programme, which aims to provide evidence-based policy on workforce development, mapped against FIP’s 21 Development Goals. This report highlights systems, tools and mechanisms available to support global workforce transformation, in line with the FIP Brisbane Calls to Actions launched on the fifth anniversary of the 2018 Astana Declaration on Primary Health Care. The work to produce this report undertook a mixed methods approach, comprising surveys, alongside stakeholder and leadership interviews with national leadership bodies to collect data. Among the key findings are that a majority of ongoing priorities and programmes delivered by the leadership organisations are related to people-centred care and patient safety, indicating a strong commitment to improving the quality of pharmaceutical healthcare services. However, there are ongoing challenges in maintaining a sufficient and sustainable supply of pharmacy professionals and there is a clear need to enhance advanced and specialist training worldwide. The findings also indicate needs and opportunities to support workplace-based education and training and the use of professional portfolios. “Our findings highlight the importance of capacity building and competency development in improving the overall quality of pharmaceutical healthcare delivery. The next phase of this project will involve design and delivery of an education and training intervention, and its evaluation. Further evaluations to identify global gaps and needs will be conducted,” Prof. Bates said.

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

HIT BACK AGAINST CROHN’S DISEASE WITH RINVOQ®▼ (upadacitinib)

PRESCRIBING INFORMATION (PI). RINVOQ®▼ ▼ (upadacitinib) 15 mg prolonged release tablets; 30mg prolonged-release tablets; 45 mg prolonged-release tablets. Refer to Summary of Product Characteristics (SmPC) for full prescribing information. PRESENTATION: Each tablet contains upadacitinib hemihydrate, equivalent to 15mg of upadacitinib in the 15mg tablet, 30mg in the 30mg tablet and 45mg in the 45mg tablet. INDICATION: Treatment of moderate to severe active rheumatoid arthritis (RA) and active psoriatic arthritis (PsA) in adult patients who have responded inadequately to, or who are intolerant to one or more diseasemodifying anti-rheumatic drugs (DMARDs). RINVOQ may be used as monotherapy or in combination with methotrexate. Treatment of active non-radiographic axial spondyloarthritis (nr-axSpA) in adult patients with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI), who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs). Treatment of active ankylosing spondylitis (AS) in adult patients who have responded inadequately to conventional therapy. Treatment of moderate to severe atopic dermatitis (AD) in adults and adolescents 12 years and older who are candidates for systemic therapy. Treatment of adult patients with moderately to severely active ulcerative colitis (UC) or moderately to severely active Crohn’s disease (CD) who have had an inadequate response, lost response or were intolerant to either conventional therapy or a biologic agent. DOSAGE AND ADMINISTRATION: Intended for use under guidance and supervision of a physician experienced in diagnosis and treatment of conditions for which upadacitinib is indicated. Dosage: RA, PsA, AS, and nr-axSpA: Recommended oral dose is 15mg once daily. Consideration should be given to discontinuing treatment in patients with AS and nr-axSpA who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks. AD: Adults: Recommended oral dose is 15 mg or 30 mg once daily based on individual patient presentation (see SmPC for details). A dose of 15 mg is recommended for patients at higher risk of venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy. The lowest effective dose to maintain response should be used. For patients ≥ 65 years of age, the recommended dose is 15mg once daily. Adolescents from 12 to 17 years weighing at least 30 kg: Recommended oral dose is 15mg once daily. Consideration should be given to discontinuing upadacitinib treatment in any patient who shows no evidence of therapeutic benefit after 12 weeks of treatment. UC: Induction; Recommended oral dose is 45mg once daily for 8 weeks. For patients who do not achieve therapeutic benefit by week 8, 45mg once daily may be continued for an additional 8 weeks. Discontinue treatment in patients with no evidence of therapeutic benefit by week 16. Maintenance; Recommended oral dose is 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). A dose of 15 mg is recommended for patients at higher risk of VTE, MACE and malignancy. The lowest effective dose to maintain response should be used. Patients ≥ 65 years of age: recommended dose is 15 mg once daily. In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care. For patients with UC receiving strong inhibitors of cytochrome P450 (CYP) 3A4 the recommended induction dose is 30 mg once daily and maintenance dose is 15 mg once daily. CD: Induction; Recommended oral dose is 45mg once daily for 12 weeks. For patients who have not achieved adequate therapeutic benefit after the initial 12-week induction, 30mg once daily may be considered. For these patients, upadacitinib should be discontinued if there is no evidence of therapeutic benefit after 24 weeks of treatment. Maintenance; Recommended oral dose is 15mg or 30mg once daily based on individual patient presentation (see SmPC for details). A dose of 15mg once daily is recommended for patients at higher risk of VTE, MACE and malignancy. The lowest effective dose to maintain response should be used. Patients ≥ 65 years of age: recommended dose is 15 mg once daily. In patients who have responded to treatment with upadacitinib, corticosteroids may be reduced and/or discontinued in accordance with standard of care. For patients with CD receiving strong inhibitors of cytochrome P450 (CYP) 3A4 the recommended induction dose is 30 mg once daily and maintenance dose is 15 mg once daily. (see SmPC for more details). Special Populations: Elderly: Upadacitinib should only be used in patients ≥65 years if no suitable treatment alternatives are available. For AD patients ≥ 65 years of age, a dose higher than 15mg once daily is not recommended. For RA, PsA, AS and nraxSpA there are limited data for patients 75 years of age and older. For UC and CD maintenance therapy, a dose higher than 15 mg once daily is not recommended in patients ≥ 65 years of age. For UC and CD patients ≥ 75 years of age the safety and efficacy of upadacitinib has not been established. Renal: No dose adjustment required in mild-moderate renal impairment. Patients with severe renal impairment should use upadacitinib with caution (See SmPC for dose adjustments). Upadacitinib has not been studied in subjects with end stage renal disease and is therefore not recommended for use in these patients. Hepatic impairment: No dose adjustment is required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Should not be used in patients with severe (Child Pugh C) hepatic impairment. Paediatric Population: Safety and efficacy in RA, AS, PsA, nr-axSpA, UC and CD in children and adolescents aged 0 to 18 years and in AD in children under 12 years of age has not been established. No clinical exposure data are available in AD adolescents < 40 kg. CONTRAINDICATIONS: Hypersensitivity to active substance or excipients. Active tuberculosis (TB) or active serious infections. Severe hepatic impairment. Pregnancy. SPECIAL WARNINGS AND PRECAUTIONS: See SmPC for full details. Upadacitinib should only be used if no suitable treatment alternatives are available in patients: 65 years of age and older; with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers) or with malignancy risk factors (e.g. current malignancy or history of malignancy). Immunosuppression: Combination use, with immunosuppressants e.g. azathioprine, 6-mercaptopurine, ciclosporin, tacrolimus, and biologic DMARDs or other JAK inhibitors has not been evaluated in clinical studies and is not recommended as the risk of additive immunosuppression cannot be excluded. Serious infections: Serious and fatal infections have been reported. Caution when treating patients ≥65 years. Frequently reported – pneumonia and cellulitis. Bacterial meningitis and sepsis have been reported. Opportunistic infections reported – TB, multidermatomal herpes zoster, oral/oesophageal candidiasis, and cryptococcosis. Do not initiate treatment in patients with active, serious infection, including localised infections. Consider the risk/benefit of treatment in patients with: chronic or recurrent infection, history of serious or opportunistic infection, those exposed to TB, those who have resided or travelled in areas of endemic TB or endemic mycoses, those with underlying conditions that may pre-dispose patients to infection, those with

diabetes. Closely monitor patients for signs and symptoms of infection during and after treatment. Interrupt treatment if the patient develops a serious/opportunistic infection. If infection is controlled, resume treatment following risk/benefit consideration. A higher rate of serious infections was observed with upadacitinib 30mg compared to upadacitinib 15mg. Tuberculosis: Pre-screen patients for active or latent TB. RINVOQ should not be given to patients with active TB. Consider anti-TB therapy in patients with previously untreated latent TB or in patients with risk factors for TB infection. Consult with a physician with experience in TB therapy to assess whether initiating anti-TB therapy is appropriate for an individual patient. Monitor patients for the development of signs and symptoms of TB, including patients who tested negative for latent TB infection prior to initiating therapy. Viral reactivation: Cases of herpes virus reactivation have been reported e.g. herpes zoster. If herpes zoster is reactivated, consider interruption of upadacitinib therapy until the episode resolves. Screen for viral hepatitis and monitor regularly for reactivation before starting and during therapy with upadacitinib. Patients, positive for hepatitis C antibody/hepatitis C virus RNA and hepatitis B surface antigen/hepatitis B virus DNA were excluded from clinical studies. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted. Vaccination: Use of live, attenuated vaccines during or immediately prior to therapy is not recommended. It is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations prior to starting therapy, in agreement with current immunisation guidelines. Malignancy: Lymphoma, NMSCs and other malignancies have been reported in patients receiving JAK inhibitors, including upadacitinib. There is a higher rate of malignancies and NMSCs with upadacitinib 30mg compared to 15mg. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. See SmPC for full details. Haematological abnormalities: Do not start therapy if Absolute Neutrophil Count <1 x 109 cells/L, Absolute Lymphocyte Count <0.5 x 109 cells/L and Hb <8 g/dL. Monitor patients and temporarily stop therapy if abnormal haematological parameters as specified are detected during routine patient management. Gastrointestinal perforations: Events of diverticulitis and gastrointestinal perforations have been reported. Use with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or opioids). Patients with active Crohn’s disease are at increased risk for developing intestinal perforation. Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. Major adverse cardiovascular events: Events of MACE were observed in clinical studies of upadacitinib (See SmPC for full details). Lipids: Monitor total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) at 12 weeks and thereafter according to international guidelines for hyperlipidaemia. Elevated LDL in clinical trials decreased to pre-treatment levels in response to statin therapy, although evidence is limited. The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Hepatic transaminase elevations: Monitor liver enzymes at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. In such cases therapy should be interrupted until this diagnosis is excluded. Venous thromboembolism: Deep vein thrombosis (DVT) and pulmonary embolism (PE) were observed in clinical trials for upadacitinib. Use therapy with caution in patients with known VTE risk factors other than cardiovascular or malignancy risk factors. Risk factors include previous VTE, patients undergoing major surgery, immobilisation, use of combined hormonal contraceptives or hormone replacement therapy, and inherited coagulation disorder. Patients should be re-evaluated periodically during upadacitinib treatment to assess for changes in VTE risk and treatment should be discontinued in patients with suspected VTE. Hypersensitivity: Anaphylaxis and angioedema have been reported in patients receiving upadacitinib. Discontinue treatment and institute appropriate therapy if significant hypersensitivity occurs. INTERACTIONS: Upadacitinib is metabolised mainly by CYP3A4 and plasma exposures may be affected by CYP3A4 inhibitors or inducers. Upadacitinib 15 mg once daily should be used with caution in patients receiving chronic treatment with strong CYP3A4 inhibitors. Upadacitinib 30 mg once daily dose is not recommended for patients with atopic dermatitis receiving chronic treatment with strong CYP3A4 inhibitors. For patients with ulcerative colitis or Crohn’s disease using strong CYP3A4 inhibitors, the recommended induction dose is 30 mg once daily and the recommended maintenance dose is 15 mg once daily (see Dosage and Administration). Avoid food and drink containing grapefruit during treatment with upadacitinib. See SmPC for full details. FERTILITY, PREGNANCY AND LACTATION: Upadacitinib is contraindicated during pregnancy. Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of upadacitinib. Female paediatric patients and/or their parents/caregivers should be informed about the need to contact the treating physician once the patient experiences menarche while taking upadacitinib. Upadacitinib should not be used during breast-feeding. The effect of upadacitinib on human fertility has not been evaluated. ADVERSE REACTIONS: Refer to SmPC for full details on adverse reactions. Very common adverse reactions (≥1/10): upper respiratory tract infections, acne. Common adverse reactions (≥1/100 to <1/10): bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, urinary tract infection, pneumonia, non-melanoma skin cancer, anaemia, neutropaenia, lymphopaenia, urticaria, hypercholesterolaemia, hyperlipidaemia, cough, abdominal pain, nausea, rash, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance; website: www.hpra.ie. LEGAL CLASSIFICATION: POM (S1A). MARKETING AUTHORISATION NUMBER/ PRESENTATION: EU/1/19/1404/001: RINVOQ 15 mg prolonged-release tablets in cartons of 28 tablets; EU/1/19/1404/006: RINVOQ 30 mg prolonged-release tablets in cartons of 28 tablets; EU/1/19/1404/010: RINVOQ 45 mg prolonged-release tablets in cartons of 28 tablets. MARKETING AUTHORISATION HOLDER: AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24, Ireland. DATE OF REVISION: April 2023. PI-1404-010. IE-RNQG-230025 | July 2023

12 News

New Leadership Team at Medicines for Ireland

Negotiation on the new Framework Agreement on Supply and Pricing of Medicines set to be a key priority for incoming Medicines for Ireland chair and vice-chair

“The EU Pharmaceutical Package is an important development that will have major impacts on the Irish landscape”

Medicines for Ireland (MFI) has appointed Paul Neill, Director of Generic Medicines, Teva Pharmaceuticals Ireland and Melissa Fisher, Country Manager, Viatris, as its new Chairperson and Vice Chairperson. Mr Neill and Ms Fisher take on their new roles at a pivotal time in the generic and biosimilar industry as it prepares for negotiation with the Department of Health on the new Framework Agreement on Supply and Pricing of Medicines.

Since its foundation in 2016, MFI has been promoting the benefits of the increased use of generic and biosimilar medicines in Ireland. The organisation’s core objective is to improve how Ireland procures and supplies medicines to expand patient access to affordable, lifesaving and life-enhancing treatment, all while generating significant value for the State. Speaking ahead of his appointment as MFI chair at the

association’s AGM, Mr Neill said: “Our association and members have embraced the opportunity to bring about significant positive change in healthcare accessibility and affordability. As the Irish healthcare budget remains under significant pressure, generic medicines can offer substantial value for both healthcare systems and patients. While the demand for cost-effective medications has risen in Ireland in recent years, there remains significant scope to increase usage of generic medicines to align with the UK and EU.” “To truly achieve the great possibilities our forward-thinking industry can provide, we must

ensure strong and progressive relationships with the state, including politicians, state bodies, and European partners. These relationships are vital in shaping policies that support a better and more cohesive ecosystem that benefits patients, healthcare systems and the state,” he concluded. Ahead of her appointment as vice-chair, Ms Fisher said: “The challenges of our time require innovative solutions developed and informed by all key stakeholders across the medicines supply chain. MFI stands at the forefront of advocating for policies that promote a stronger, collaborative, and innovative landscape in which generic and biosimilar medicines play an even more significant role in enhancing patient and healthcare system outcomes. “The EU Pharmaceutical Package is an important development that will have major impacts on the Irish landscape. MFI members will continue to collaborate with our European counterparts in Medicines for Europe to ensure it is the best possible package for patients and the healthcare system in Ireland. This will be a key for us when we welcome our colleagues from Medicines for Europe to Ireland for the industry’s annual general assembly in June 2024,” she concluded.

Hospital Pharmacists on addressing Medicine Shortages The European Association of Hospital Pharmacists (EAHP) has welcomed the Communication on medicine shortages adopted by the European Commission (EC), as well as The Executive Steering Group on Shortages and Safety of Medicinal Products (MSSG) Toolkit on recommendations on tackling shortages of medicinal products and MSSG Solidarity Mechanism adopted by the EMA.

should be established in a way that all stakeholders may contribute to its functionality and secure the transparency of information fed in and exported out of the platform. Therefore, EAHP welcomes its launch in 2025 and hope that it will prove to be useful particularly for healthcare professionals seeking for an appropriate information on shortages.

EAHP has been exploring the multifaceted nature of medicine shortages for more than a decade and providing recommendations to mitigate shortages and their impact on patients' outcome as seen in the latest EAHP 2023 Shortage Survey Report.

EAHP welcomes the creation of Critical Medicines Alliance, but believes that apart from national authorities, industry, civil society representatives, the Commission and EU agencies, healthcare professional associations should also be given the possibility to come together with the aforementioned stakeholders to develop coordinated action at EU level to tackle shortages.

EAHP has been reiterating for years that the European Shortages Monitoring Platform

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Moreover, EAHP believes that the Commission's Structured Dialogue demonstrated the complex nature of establishing the “criticality” of a medicine and different approaches to appoint the level of criticality. Therefore, EAHP suggests that beside the availability of alternatives and the therapeutic indication of the medicines, as parameters of criticality, patient clinical status and needs assessment performed by healthcare professionals, should also be considered when assigning the criticality of the medicine affected by the shortages. EAHP welcomes the recommendations on mitigating supply chain vulnerabilities and tailoring joint procurement strategies, as well as creating safety stocks of medicines and medical devices. While

EAHP believes that supply and demand forecasting is essential in avoiding shortages, the transparency of information given by all stakeholders involved in supply chain and healthcare provision is essential and it does not either lean only on supply or demand side of shortages. Moreover, EAHP is in favor of addressing challenges with the API production through its diversification and strengthening to avoid a major safety concern for the entire supply chain, as stated in the Communication. EAHP supports the creation of the Union list of critical medicines, created together with healthcare professional associations' representatives to avoid the creating of an incomplete list, which will not encompass all medicines deemed critical.

Choose Cosentyx today, to protect your psoriasis patients tomorrow1-4

1 million patients treated5

No new safety signals identified in clinical trials or the real world6,7

YRS

on the market in Ireland8 ABBREVIATED PRESCRIBING INFORMATION Please refer to the Summary of Product Characteristics (SmPC) before prescribing. COSENTYX (secukinumab) Presentations: Cosentyx 150 mg solution for injection in pre-filled pen and Cosentyx 300 mg solution for injection in pre-filled pen. Therapeutic Indications: The treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy; the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of 6 years who are candidates for systemic therapy; the treatment of active moderate to severe hidradenitis suppurativa (acne inversa) in adults with an inadequate response to conventional systemic HS therapy; the treatment, alone or in combination with methotrexate (MTX), of active psoriatic arthritis in adult patients when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate; the treatment of active ankylosing spondylitis in adults who have responded inadequately to conventional therapy; the treatment of active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence in adults who have responded inadequately to non-steroidal antiinflammatory drugs (NSAIDs); alone or in combination with methotrexate (MTX), the treatment of active enthesitis-related arthritis in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy; alone or in combination with methotrexate (MTX), the treatment of active juvenile psoriatic arthritis in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy. Dosage & Method of Administration: Adult Plaque Psoriasis: 300 mg given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. Dosing at Weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Based on clinical response, a maintenance dose of 300 mg every 2 weeks may provide additional benefit for patients with a body weight of 90 kg or higher. Paediatric Plaque Psoriasis: The recommended dose is based on body weight (see Table 1 in SmPC for full details) and administered by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Each 75 mg dose is given as 1 subcutaneous injection of 75 mg. Each 150 mg dose is given as 1 subcutaneous injection of 150 mg. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as 2 subcutaneous injections of 150 mg. The 150 mg and 300mg solution for injection in pre-filled syringe and pre-filled pens are not indicated for administration to paediatric patients with a weight <50 kg. Hidradenitis suppurativa (HS): The recommended dose is 300 mg of secukinumab by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3, and 4, followed by monthly maintenance dosing. Based on clinical response, the maintenance dose can be increased to 300 mg every 2 weeks. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. Psoriatic Arthritis: For patients with concomitant moderate to severe plaque psoriasis, please refer to adult plaque psoriasis recommendation. For patients who are anti-TNFα inadequate responders, the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Each 300 mg dose is given as one subcutaneous injection of 300 mg or as two subcutaneous injections of 150 mg. For all other patients, the recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Based on clinical response, the dose can be increased to 300 mg. Ankylosing Spondylitis (AS, radiographic axial spondyloarthritis): The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 3 and 4, followed by monthly maintenance dosing. Based on clinical response, the dose can be increased to 300 mg. Non-radiographic axial spondyloarthritis (nraxSpA): The recommended dose is 150 mg by subcutaneous injection with initial dosing at weeks 0, 1, 2, 3 and 4, followed by monthly maintenance dosing. Juvenile idiopathic arthritis (JIA): Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA): The recommended dose is based on body weight (see Table 2 in SmPC for full details) and administered by subcutaneous injection at weeks 0, 1, 2, 3, and 4, followed by monthly maintenance dosing. Each 75 mg dose is given as one subcutaneous injection of 75 mg. Each 150 mg dose is given as one subcutaneous injection of 150 mg. The 150 mg and 300 mg solution for injection in pre-filled syringe and in pre-filled pen are not indicated for administration to paediatric patients with a weight <50 kg. Cosentyx may be available in other strengths and/or presentations depending on the individual treatment needs. For all of the above indications, available data suggest that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response up to 16 weeks of treatment. Some patients with initially partial response may subsequently improve with continued treatment beyond 16 weeks. The safety and efficacy of Cosentyx in children with plaque psoriasis and in the juvenile idiopathic arthritis (JIA) categories of ERA and JPsA below the age of 6 years have

not been established.The safety and efficacy in children below the age of 18 years in other indications have not yet been established. Contraindications: Severe hypersensitivity reactions to the active substance or to any of the excipients. Clinically important, active infection (e.g. active tuberculosis). Warnings/Precautions: Infections: Secukinumab has the potential to increase the risk of infections. Serious infections have been observed in patients receiving secukinumab in the post-marketing setting. Infections observed in clinical studies are mainly mild or moderate upper respiratory tract infections such as nasopharyngitis not requiring treatment discontinuation. Non-serious mucocutaneous candida infections more frequently reported for secukinumab than placebo in psoriasis clinical studies. Caution in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, close monitoring and discontinue treatment until the infection resolves. Should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation in patients with latent tuberculosis. Inflammatory bowel disease: Cases of new or exacerbations of inflammatory bowel disease have been reported with secukinumab. Secukinumab is not recommended in patients with inflammatory bowel disease. If a patient develops signs and symptoms of inflammatory bowel disease or experiences an exacerbation of pre-existing inflammatory bowel disease, secukinumab should be discontinued and appropriate medical management should be initiated. Hypersensitivity reactions: In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving secukinumab. If an anaphylactic or other serious allergic reactions occur, administration should be discontinued immediately and appropriate therapy initiated. Latex-sensitive individuals: The removable cap of the Cosentyx pre-filled pen contains a derivative of natural rubber latex. Vaccinations: Live vaccines should not be given concurrently with secukinumab. Patients may receive concurrent inactivated or non live vaccinations. Prior to initiating therapy with Cosentyx, it is recommended that paediatric patients receive all age appropriate immunisations as per current immunisation guidelines. Concomitant immunosuppressive therapy: Use in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated. Interactions: Live vaccines should not be given concurrently with secukinumab. In a study in adult subjects with plaque psoriasis, no interaction was observed between secukinumab and midazolam (CYP 3A4 substrate. No interaction seen when administered concomitantly with methotrexate (MTX) and/or corticosteroids. Caution should be exercised when considering concomitant use of other immunosuppressants and secukinumab. Fertility, Pregnancy and Lactation: Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment. It is preferable to avoid the use of Cosentyx in pregnancy as there are no adequate data from the use of secukinumab in pregnant women. It is not known whether secukinumab is excreted in human milk. A decision on whether to discontinue breast feeding during treatment and up to 20 weeks after treatment or to discontinue therapy with Cosentyx must be made taking into account the benefit of breast-feeding to the child and the benefit of Cosentyx therapy to the woman. The effect of secukinumab on human fertility has not been evaluated. Undesirable Effects: Very common (≥1/10); Upper respiratory tract infections. Common (≥1/100 to <1/10); Oral herpes, rhinorrhoea, diarrhoea, fatigue, nausea and headache Uncommon (≥1/1,000 to <1/100); Oral candidiasis, otitis externa, urticaria, neutropenia, dyshidrotic eczema, conjunctivitis, lower respiratory tract infections, tinea pedis and inflammatory bowel disease. Rare (≥1/10,000 to <1/1,000); Anaphylactic reactions, exfoliative dermatitis and hypersensitivity vasculitis. Unknown: Mucosal and cutaneous candidiasis (including oesophageal candidiasis) and pyoderma gangrenosum. Please see Summary of Product Characteristics for further information on undesirable effects. Legal Category: POM. Marketing Authorisation Holder: Novartis Europharm Ltd, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland. Marketing Authorisation Numbers: EU/1/14/980/004 and EU/1/14/980/010. Prescribing Information last revised: May 2023. Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Elm Park, Dublin 4. 01-2601255 or at www.medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk profile of the medicinal product. All suspected adverse reactions should be reported to HPRA Pharmacovigilance at www.hpra.ie. Adverse events can also be reported to Novartis preferably at www.novartis.com/report, by emailing drugsafety.dublin@novartis. com or by calling (01) 2080 612.

References: 1. Sigurgeirsson B et al. Dermatol Ther. 2022;35(3):e15285. 2. Bissonnette R et al. J Eur Acad Dermatol Venereol. 2018;32(9):1507-1514. 3. McInnes IB et al. Lancet Rheumatol. 2020;2(4):e227-e235. 4. McInnes IB et al. Rheumatology (Oxford). 2017;56(11):1993-2003. 5. Novartis Data on File. Cosentyx Patient Reach Feb 2023. 6. Novartis Data on File RWE Compendium Sept2021-Mar2022. 7. Gottlieb AB, et al. Acta Derm Venereol. 2022. doi: 10.2340/actadv.v102.563. 8. NCPE Secukinumab (Cosentyx®) Assessment | National Centre for Pharmacoeconomics Accessed Mar 2023. July 2023 I IE296850

14 Drug Overdosing

Preventing intentional drug overdose with paracetamol What we can do together Content warning: This article contains sensitive information on self-harm, which some readers may find triggering. Any readers particularly affected by this content are advised to link with a supervisor or allied supports available. Additional supports are listed at the end of this article. Written by: Dr Caroline Daly, Postdoctoral Researcher, National Suicide Research Foundation and Paracetamol WG Co-ordinator Dr Michelle O’Driscoll, Postdoctoral Researcher National Suicide Research Foundation and Paracetamol WG Co-ordinator

Dr Caroline Daly

Prof. Philip Dodd, Consultant Psychiatrist/Clinical Professor, Mental Health Policy & Clinical Specialist at the Department of Health, Mental Health Unit, Clinical Advisor of National Office for Suicide Prevention and Paracetamol WG Co-Chair.

Paracetamol intentional drug overdose

Dr Michelle O’Driscoll

Paracetamol is the drug most frequently taken in intentional and accidental overdose in Ireland. Each year the National SelfHarm Registry Ireland (NSHRI) records approximately 2,300 hospital-presenting intentional drug overdoses with paracetamol, with rates increasing among young people.1,2 For every male overdose with paracetamol there are four female paracetamol IDOs.

Prof. Philip Dodd

Pictured at the launch of the campaign are Minister Mary Butler TD (Minister for Mental Health and Older People), and representatives from the Department of Health, National Suicide Research Foundation, HSE National Office for Suicide Prevention, Medicines Unit (DOH) and Irish Pharmacy Union (IPU)

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Many paracetamol overdoses are clinically serious, and the physical consequences of overdoses occur in parallel with social and psychosocial impacts on individuals and their wider circles.

Restricting access to means Restricting access to means of self-harm, including paracetamol overdose, is the single most effective prevention measure. Statutory pack size and sales

15 legislation introduced in Ireland since 2001 have led to a decrease in deaths involving paracetamol and a reduction in the toxicity of overdoses.4 However, research has shown that adherence to this legislation is poor.5 Preventing Paracetamol-Related Drug Overdose Working Group (WG) To address this issue, the Preventing Paracetamol-Related Drug Overdose Working Group (WG) led by the Department of Health was established in 2021 to decipher next steps to prevent intentional paracetamol overdose in Ireland. This works supports the implementation of Connecting for Life, Ireland’s National Strategy to Reduce Suicide (2015-2024), and specifically action 6.1.2, ‘continue improvements in adherence to the legislation limiting access to paracetamol through raising awareness amongst retailers and the public and the use of point ofsale systems.’ The group has representation from the Department of Health, the HSE National Office for Suicide Prevention (NOSP), the Health Products Regulatory Authority (HPRA), the National Suicide Research Foundation (NSRF), the Pharmaceutical Society of Ireland (PSI) and support from retail stakeholders. The Group aims to enhance information and support training development for pharmacy and non-pharmacy retail sector staff, collaborate on preventative interventions, and support actions required following market surveillance work.

New information campaign Following extensive consultation, and a nationwide survey of pharmacy and non-pharmacy retail staff, new educational materials were launched by Minister Mary Butler on behalf of the working group on 17th October 2023 at the Department of Health. These educational materials highlight the purpose of the legislation and how to raise awareness of regulations amongst those who sell paracetamol to the public. This will ultimately contribute to the prevention of paracetamol related intentional drug overdose in Ireland. As part of this campaign, new information packs are now available to order or download for pharmacy settings. They contain informative posters and postcards suitable for display in staff areas or noticeboards. They also contain shelf-riders/stickers that might be suitable for public-facing or staff-facing display units where paracetamol-containing products are displayed. Additional icons are available in .jpg and .png formats that could be suitable for inclusion on, for example websites, or email signatures. Get your information packs Two versions of information packs are available – one for Pharmacy retail settings and staff, and one for non-Pharmacy general retail settings and online (for example convenience stores, supermarkets, service stations).

of pharmacy and non-pharmacy retail staff on restrictions in place for paracetamol-containing medicines. We all have a role to play in the reduction of the incidence of paracetamol-related intentional drug overdose in Ireland, and so we encourage pharmacies to engage in this information campaign, and utilise the tools available to increase awareness and knowledge among staff and the public.” Follow the QR code or visit https://www.hse.ie/eng/services/ list/4/mental-health-services/ connecting-for-life/publications/ safe-sales-of-paracetamol.html – where the information packs are now available: • To order for free delivery • To download. Further information Contact the HSE National Office for Suicide Prevention (NOSP) at info@nosp.ie if: • You would like to adapt any of these materials for other uses (for example incorporating the information with your own branding or pharmacy signage), or • You have any questions or feedback on these information packs. The CEO/Registrar of the Pharmaceutical Society of Ireland (PSI), Joanne Kissane said of the campaign. “This information and awareness campaign is an important milestone in the ongoing work of the multi-stakeholder, collaborative Working Group. The PSI are happy to be a part of this work, which is intended to highlight the importance of appropriate paracetamol sales to protect public safety, and support the education

For further information in relation to the Working Group and this campaign, please contact Dr Michelle O’Driscoll at michelle.odriscoll@ucc.ie. Literature 1. Joyce M, Daly C, McTernan N, Griffin E, Nicholson S, Arensman E, Williamson E, Corcoran P. (2020) National Self-Harm Registry Ireland Annual Report 2019. Cork: National Suicide Research Foundation. 2. Daly C, Griffin E, McMahon E, Corcoran P, Webb RT, Ashcroft DM, Arensman E. (2020) Paracetamolrelated intentional drug overdose among young people: a national registry study of characteristics, incidence and trends, 2007-2018. Soc Psychiatry Psychiatr Epidemiol. 56(5):773-81. 3. Gulmez SE, Larrey D, Pageaux GP, Bernuau J, Bissoli F, Horsmans Y, Thorburn D, McCormick PA, Stricker B, Toussi M, Lignot-Maleyran S, Micon S, Hamoud F, Lassalle R, Jové J, Blin P, Moore N. Liver transplant associated with paracetamol overdose: results from the sevencountry SA LT study. Br J Clin Pharmacol. 2015; 80: 599-606 4. Donohoe E, Walsh N, Tracey JA. Pack-size legislation reduces severity of paracetamol overdoses in Ireland. Ir J Med Sci. 2006;175(3):40-2. 5. Ni Mhaolain AM, Davoren M, Kelly BD, Breen E, Casey P. (2009) Paracetamol availability in pharmacy and non-pharmacy outlets in Dublin. Ireland. Ir J Med Sci. 178(1):79–82.

Support information - If you, or someone you know, needs mental health support or a listening ear, reach out to a trusted service. Many are available 24/7 and you can make contact in different ways, for example: • on the phone – Samaritans – freephone 116 123 • by text message - Text About It – text HELLO to 50808 • online – MyMind - www.mymind.org • face-to-face – Pieta – freephone 1800 247 247 You can also call the HSE YourMentalHealth Information Line, anytime day or night, for information on mental health, and what other services and supports are available near you. Freephone 1800 111 888 or visit www.yourmentalhealth.ie.

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

16 News

Biosimilars ‘Critical’ for Future Medicine Access By 2032, the biosimilar medicines contribution to health systems access and sustainability will soon match the impact of generic medicines. The number of biological medicines set to lose market exclusivity represents an opportunity for competition to free up invaluable resources for healthcare systems, to improve patient access and budget sustainability. The 2023 update of the IQVIA report ‘The Impact of Biosimilar Competition in Europe’, presented recently at the European Commission annual stakeholder event, describes the evolution of the biopharmaceutical market following the arrival of biosimilar competition in Europe.

It underlines the considerable cumulated clinical experience gathered with biosimilar medicines, reaching 5.8 billion patient treatment days, and the considerable contribution of biosimilar medicines to healthcare sustainability with ¤50 billion cumulated savings. The widening of access inequity across EU member states, in spite of biosimilar medicines availability is a major concern which requires more multi-stakeholder policy work to benefit from the next wave of biologic Loss of Exclusivity. Commenting ahead of the European Commission meeting, Julie Maréchal-Jamil, Director of Biosimilars Policy & Science at Medicines for Europe, said, “Today, the positive contribution

of biosimilar medicines to availability, affordability, accessibility and innovation needs no further demonstration. With the next wave of biotechnological medicines around the corner, we need a fundamental redirection of regulatory and market approaches if we want to expand patient access to more biologic medicines. Coordinated action at EU and national level can undoubtedly contribute to address today’s disparities and changing dynamics.” The annual European Commission multistakeholder biosimilar event offers a unique opportunity for open and constructive dialogue among actors of the biosimilar field and acts as reference point for the European biosimilar policy agenda.

The Biosimilar Medicines Group is a sector group of Medicines for Europe representing the leading companies developing, manufacturing and/or marketing biosimilar medicines across Europe. With more than 15 years of positive patient treatment experience, biosimilar medicines today provide a huge opportunity to deliver significantly improved access to modern therapies for millions of European patients in both chronic and acute care. The members bring competition to the biological medicines market, thereby increasing access to highly innovative treatments to patients in Europe and around the world, and supporting the sustainability of the European healthcare systems.

Tallaght to increase Endoscopy Procedures Professor Colm O’Móráin

The new Colm O’Móráin Centre for Digestive Diseases within the Hospital will encompass the Endoscopy & Gastroenterology Departments at TUH, which have developed innovative new services such as Dietitian-led Gut Therapy for IBS, Hi-Resolution Oesophageal Physiology, Liver Elastography and being established as the national lead centre for Capsule Endoscopy and the study of H.pylori resistance.

Tallaght University Hospital (TUH) has announced plans to carry out an additional 4,300 endoscopy procedures a year. These will take place in the newly opened Colm O’Móráin Centre for Digestive Diseases. The new development which is located within the Hospital, represents an overall investment of over ¤1.7m.

TUH has been able to open this new unit by repurposing space which became free after day surgeries (where patients return home the same day) were moved into a brand new surgical facility, just opposite the Hospital in Tallaght called the Reeves Day Surgery Centre (RDSC).

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Prof Anthony O’Connor Clinical Lead of the Department of Gastroenterology at TUH says, “Professor Colm O’Móráin, was one of the greatest Irish clinicianscientist of his or any era, a true trail blazer who established the gastroenterology unit here where he worked for many years before retiring from the Hospital in 2011, however he still provides leadership working

full-time as the director of the HSE National Clinical Programme for Gastroenterology. Among other achievements, Professor O’Móráin was the first to prove that Duodenal ulcers could be cured by antibiotics and later in his career started bowel screening in Ireland, which was piloted here in Tallaght before being rolled out nationally. It is both a great privilege and a responsibility for us to carry his legacy by continuing the great work he started in the new centre we are naming in his honour today.” Welcoming the new development, Professor Colm O’Móráin said, “I am delighted to see the continued expansion of such an important diagnostic services at TUH. It is reassuring to know that the physicians based here will have the latest in cutting edge endoscopy diagnostics to enable them to design the best and most appropriate treatments for patients. I am humbled that this new centre has been named after me. It is a great honour.” Professor O Móráin is the National Clinical lead for Gastroenterology and Hepatology in Ireland. He is an Emeritus Professor of Medicine and a former Dean of the Faculty of Health Sciences at Trinity College Dublin. He has published over 500 scientific papers and authored or co-authored six books. His research interest are Helicobacter Inflammatory Bowel Disease and Colorectal Cancer Screening.

This is a promotional advertisement from LEO Pharma for IE healthcare professionals. For the treatment of moderate to severe atopic dermatitis in adult and adolescent patients 12 years and older who are candidates for systemic therapy1

TIME TO PRESS PLAY Not an actual patient. For illustrative purposes only. Individual results may vary.

Adtralza®

The first licensed biologic that inhibits IL-13 alone,1,2 a key driver of atopic dermatitis signs and symptoms.3 Learn more at www.adtralza.ie Prescribing Information for Adtralza® (tralokinumab) 150 mg solution for injection in pre-filled syringe Please refer to the full Summary of Product Characteristics (SmPC) (www.medicines.ie) before prescribing. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Indications: Treatment of moderate-tosevere atopic dermatitis in adult and adolescent patients 12 years and older who are candidates for systemic therapy. Active ingredients: Each pre-filled syringe contains 150 mg of tralokinumab in 1 mL solution (150 mg/mL). Dosage and administration: Posology: The recommended dose of tralokinumab for adult and adolescent patients 12 years and older is an initial dose of 600 mg (four 150 mg injections) followed by 300 mg (two 150 mg injections) administered every other week as subcutaneous injection. Every fourth week dosing may be considered for patients who achieve clear or almost clear skin after 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve further with continued treatment every other week beyond 16 weeks. Tralokinumab can be used with or without topical corticosteroids. The use of topical corticosteroids, when appropriate, may provide an additional effect to the overall efficacy of tralokinumab. Topical calcineurin inhibitors may be used, but should be reserved for problem areas only, such as the face, neck, intertriginous and genital areas. If a dose is missed, the dose should be administered as soon as possible and then dosing should be resumed at the regular scheduled time. No dose adjustment is recommended for elderly patients, patients with renal impairment or patients with hepatic impairment. For patients with high body weight (>100 kg), who achieve clear or almost clear skin after 16 weeks of treatment, reducing the dosage to every fourth week might not be appropriate. The safety and efficacy of tralokinumab in children below the age of 12 years have not yet been established. Method of administration: Subcutaneous use. The pre-filled syringe should not be shaken. After removing the pre-filled syringes from the refrigerator, they should be allowed to reach room temperature by waiting for 30 minutes before injecting. Tralokinumab is administered by subcutaneous injection into the thigh or abdomen, except the 5 cm around the navel. If somebody else administers the injection, the upper arm can also be used. For the initial 600 mg dose, four 150 mg tralokinumab injections should be administered consecutively in different injection

sites within the same body area. It is recommended to rotate the injection site with each dose. Tralokinumab should not be injected into skin that is tender, damaged or has bruises or scars. A patient may self-inject tralokinumab or the patient’s caregiver may administer tralokinumab if their healthcare professional determines that this is appropriate. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Precautions and warnings: If a systemic hypersensitivity reaction (immediate or delayed) occurs, administration of tralokinumab should be discontinued and appropriate therapy initiated. Patients treated with tralokinumab who develop conjunctivitis that does not resolve following standard treatment should undergo ophthalmological examination. Patients with pre-existing helminth infections should be treated before initiating treatment with tralokinumab. If patients become infected while receiving tralokinumab and do not respond to antihelminth treatment, treatment with tralokinumab should be discontinued until infection resolves. Live and live attenuated vaccines should not be given concurrently with tralokinumab. Fertility, pregnancy and lactation: There is limited data from the use of tralokinumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of tralokinumab during pregnancy. It is unknown whether tralokinumab is excreted in human milk or absorbed systemically after ingestion. Animal studies did not show any effects on male and female reproductive organs and on sperm count, motility and morphology. Side effects: Very common (≥1/10): Upper respiratory tract infections. Common (≥1/100 to <1/10): conjunctivitis, conjunctivitis allergic, eosinophilia, injection site reaction. Uncommon (≥1/1,000 to <1/100): keratitis. Precautions for storage: Store in a refrigerator (2°C-8°C). Do not freeze. Store in the original package in order to protect from light. Legal category: POM. Marketing authorisation number and holder: EU/1/21/1554/002. LEO Pharma A/S, Ballerup, Denmark. Last revised: October 2022 Reference number: REF-22407 Reporting of Suspected Adverse Reactions Adverse events should be reported. Reporting forms and information can be obtained from: HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to Drug Safety at LEO Pharma by calling +353 1 4908924 or e-mail medical-info.ie@leo-pharma.com

IL, interleukin. References: 1. Adtralza® SPC. 2. Duggan S. Drugs 2021;81(14):1657–1663. 3. Bieber T. Allergy 2020;75:54–62.

Further information can be found in the Summary of Product Characteristics or from: LEO Pharma, Cashel Road, Dublin 12, Ireland. E-mail: medical-info.ie@leo-pharma.com ® Registered trademark

Date of preparation: December 2022 IE/MAT-62263

Respiratory - COPD

Optimising COPD Management: The Integrated Care Paradigm

Dr Dhiviya Ganesan, Respiratory Registrar, Galway University Hospital (GUH)

Dr Sinéad Walsh, Respiratory Care GUH Written by DrWalsh, Dhiviya Ganesan,Integrated Respiratory Galway University Hospital (GUH) and Dr Sinéad Respiratory IntegratedRegistrar, CareConsultant, Consultant, GUH & & Community Community Healthcare Organisation 2 2 Integrated Care Consultant, GUH & Community Healthcare Organisation 2 Dr Sinéad Walsh, Respiratory Healthcare Organisation

Dr Dhiviya Ganesan

Dr Sinéad Walsh

The most common symptom reported by patients is dyspnoea on exertion. Dyspnoea that is persistent, progressive over time and worse with exercise is characteristic of COPD. The modified Medical Research Council (mMRC) scale is a useful dyspnoea scoring system that forms part of the GOLD COPD classification system. Dyspnoea is multi-factorial in COPD. Contributing factors include airway obstruction, parenchymal destruction, dynamic hyper inflation leading to air trapping, and systemic effects including sarcopenia.

function has occurred. Tachypnoea occurs with activity, with increasing respiratory rate in proportion to disease severity. Use of accessory respiratory muscles and paradoxical indrawing of the lower intercostal spaces (Hoover sign) indicates airway hyperinflation and a flattened diaphragm. Other findings on thoracic examination include a barrel chest, hyperresonance on percussion, diffusely decreased breath sounds, and prolonged expiration. Diagnosis

Diagnosis of COPD is based on a triad of causative exposure, symptoms and spirometry. • Abnormal lung growth and Introduction Cough and sputum occur in 30% Spirometry is the most development of COPD patients. Less commonly, reproducible and objective The updated The updated 20242024 GlobalGlobal Initiative Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines patients symptoms of The updated 2024 Global Initiative forsocioeconomic Chronic Obstructive Lungdescribe Disease (GOLD) guidelines measurement of airflow limitation. for Chronic Obstructive Lung • Lower status define (GOLD) Chronic Obstructive Pulmonary Disease (COPD)wheeze, as a fatigue heterogeneous and anorexia. lung condition It measures the volume of air that guidelines defineDisease Chronic Obstructive Pulmonary Disease (COPD) as a heterogeneous lung condition Comorbidities may contribute to (bronchitis, a patient can forcibly exhale from • Asthma symptoms and airway hypercharacterized by chronic respiratory due to abnormalities of the airways define Chronic Obstructive restriction of of activity. include characterized by chronic respiratory symptoms due to abnormalities the These airways (bronchitis, the point of maximal inspiration reactivity Pulmonary Disease (COPD) as bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow heart disease, osteoporosis, (Forced Vital Capacity, FVC) and a heterogeneous lung condition bronchiolitis) and/or alveoli (emphysema) that cause persistent, progressive, airflow malignancy, often musculoskeletal • Recurrent respiratory infections the volume of air that is exhaled characterized by chronic obstruction. In this article, we review the aetiology,disorders, clinical features, diagnosis, and anxiety and depression. during and the first second of this respiratory symptoms due to obstruction. In this article, we review the aetiology, clinical features, diagnosis, Clinicalboth features of COPD management of COPD, including non-pharmacological & pharmacological interventions. manoeuvre (Forced Expiratory abnormalities of the airways The key findings on clinical management of COPD, including both non-pharmacological & pharmacological interventions. (bronchitis, bronchiolitis) and/or The main symptoms of theAssessment We will also describe the roleFigure of three Integrated CareABE in management of COPD, examination ofTool a patient withwith a paradigm 1: GOLD alveoli (emphysema) that cause are dyspnoea, chronic COPD are usually absent until We will also describe the role of COPD Integrated in the management of COPD, with a paradigm shift away from hospital-centred care to Care person-centred care. persistent, often progressive, Figure 1: GOLD ABE Assessment Tool significant impairment of lung cough, and sputum production. shift away from hospital-centred care to person-centred care. airflow obstruction. In this article, we review the aetiology, Causes of COPD clinical features, diagnosis, and management of COPD, including Causes of COPD both non-pharmacological & • Tobacco smoke pharmacological interventions. will also describe the • We Tobacco smoke • Marijuana smoking role of Integrated Care in the of COPD, with a • Indoor (household air pollution from burning solid fuels for cooking or heating) and • management Marijuana smoking paradigm shift away from hospitaloutdoor air pollution (particulate matter) • centred Indoor from burning solid fuels for cooking or heating) and care to(household person-centredair pollution care.• Occupational exposures, including dusts, chemical agents and fumes

Introduction Introduction

outdoor air pollution (particulate matter) • Occupational exposures, including dusts, chemical agents and fumes smoke • Females aresuch moreassusceptible than males to the harmful effects of cigarette smoke, • • Tobacco Genetic factors alpha-1-antitrypsin deficiency • Marijuana smokingwho smoke are 50% more likely to develop COPD than men women • Females are more susceptible than males to the harmful effects of cigarette smoke, • Indoor air pollution • (household Abnormal lung growth and development women smoke from burningwho solid fuels for are 50% more likely to develop COPD than men • Lower socioeconomic status or heating) and growth outdoor and • cooking Abnormal lung development air•pollution (particulate Asthma and matter) airway hyper-reactivity • • Occupational Lower socioeconomic status exposures, • Recurrent respiratory infections including dusts, chemical agents • Asthma and airway hyper-reactivity and fumes • • Genetic Recurrent respiratory infections factors such as alpha-1Causes COPD factors such as alpha-1-antitrypsin deficiency • ofGenetic

antitrypsinfeatures deficiency of COPD Clinical

• Females are more susceptible than males to the harmful effects Clinical features of COPD of cigarette smoke, women who smoke are 50% more likely to develop COPD than men

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Volume in one second, FEV1). The ratio of the FEV1/FVC is calculated. Airflow obstruction is a post-bronchodilator FEV1/FVC ratio less than 70%. At diagnosis, patients should have the severity of their airflow limitation classified according to the GOLD guidelines. This classifies patients with a FEV1/ FVC ratio less than 70% into four categories (GOLD 1 – 4), based on their FEV1 value. . Symptom burden is assessed using the mMRC dyspnoea score or the CAT (COPD Assessment test). An assessment of exacerbation risk should also occur. A COPD exacerbation is an acute worsening of respiratory symptoms that results in additional therapy. Exacerbations can be classified as mild, moderate or severe. The best predictor of having frequent exacerbations (defined as two or more exacerbations in one year) is a history of previous exacerbations. Using these variables, individuals may be classified as GOLD 1-4 A, B or E (Figure 1). In our practice, we obtain a chest radiograph in all new suspected COPD patients. While it does not diagnose COPD, it can be useful in excluding alternative diagnoses and establishing the presence of comorbidities including pulmonary fibrosis, pleural disease, kyphoscoliosis and cardiomegaly. We obtain routine laboratory investigations, including FBC to check for eosinophilia. Blood eosinophil counts may predict the magnitude of the effect of inhaled corticosteroid therapy as an addition to regular maintenance bronchodilator treatment in preventing future Table 1: COPD exacerbations. We screen

• • • •

Non-pharmacological Smoking cessation Physical activity Vaccine advice Pulmonary rehabilitation

for alpha one antitrypsin deficiency in concordance with WHO recommendations. For those with recurring exacerbations, we check an immunoglobulin level to screen for hypogammaglobinaemia. Management Addressing COPD treatment necessitates a comprehensive approach encompassing non pharmacological, pharmacological, and interventional therapies (Table 1). The aim of COPD management is to reduce symptoms and future risk. A particular emphasis needs to be placed on smoking cessation. Healthcare providers are pivotal in delivering smoking cessation messages and interventions. Approximately 40% of those diagnosed with COPD are active smokers, who continue to smoke despite being aware of their diagnosis. Stopping smoking is the single biggest intervention to influence the natural history of COPD. It also improves symptoms and reduces the frequency of exacerbations. Nicotine replacement therapy (NRT) is effective in promoting long-term smoking abstinence. People with COPD should be up to date with their vaccines. Current recommendations include vaccination against Influenza, SARS-CoV-2 (COVID), and pneumococcal infection. Physical activity is a strong predictor of mortality. People with COPD should be encouraged to increase their levels of physical activity. Pulmonary rehabilitation (PR), combining exercise training with disease-specific education,

• • • • • • • • •

Pharmacological NRT Inhalers – SABA, SAMA, LAMA, LABA, ICS PDE 4 inhibitor – Roflumilast Prophylactic antibiotics Mucoregulators and antioxidant agents LTOT NIV Alpha-1 antitrypsin augmentation therapy Opioids

is recommended for GOLD B – D patients and for those discharged from hospital with a COPD exacerbation. It consists of an 8-week programme of supervised incremental exercise, where patients build up their muscle strength. PR improves dyspnoea, health status and exercise tolerance in stable patients. It leads to reduced symptoms of anxiety and depression. Patients are taught breathing exercises and the benefit of pacing. A reduction in further hospitalisations by 50% for patients who had PR initiated within 4 weeks of hospitalisation for COPD, compared to those who did not have PR, has been demonstrated. Pharmacological therapy for COPD is focused on symptoms and exacerbations. Individualised treatment regimens consider factors such as symptom severity, exacerbation risk, side effects, comorbidities, drug availability, cost, patient response, preference, and ability to use drug delivery devices. As per the 2024 GOLD guidelines, the commencement of bronchodilator agent(s) or a combination of bronchodilator agents with ICS (inhaled corticosteroid) is recommended, depending on the disease severity categorized into groups A, B or E (FIGURE 2). Bronchodilator inhalers address airways obstruction, altering airway smooth muscle tone, leading to widening of the airways and improving dynamic hyperinflation. Available bronchodilators include short acting and long acting beta agonists (SABA/ LABA) and muscarinic agents (SAMA/LAMA). Rescue shortacting bronchodilators should

be prescribed to all patients for immediate symptomatic relief. Bronchodilator therapy improves dyspnoea, improve exercise performance and decrease exacerbation frequency. Combination LABA/LAMA therapy in a single inhaler demonstrates improved patient reported outcomes, compared to monotherapies alone. For Group E patients who are having frequent exacerbations combined LABA-LAMA inhaler therapy is the preferred choice for initial therapy. Use of LABA/ ICS is not encouraged. If there is an indication for the addition of an inhaled corticosteroid (ICS), then triple therapy in the form of LABA/LAMA/ICS has demonstrated superiority over LABA/ICS and should be the preferred choice. Triple therapy should be considered in Group E patients who have elevated blood eosinophil counts. If there is concomitant asthma, these patients should be treated accordingly. Under these circumstances, use of an ICS is mandatory. Regular assessment of inhaler technique is crucial. Azithromycin is a macrolide antibiotic that has anti-inflammatory effects in the airway. It can be added on to therapy in former smokers who continue to exacerbate despite maximal inhaled therapy. Roflumilast is a phosphodiesterase inhibitor that reduces inflammation in the airway but has no immediate bronchodilator effect. It may be a reasonable add-on therapy in patients with a FEV1 < 50% predicted and chronic bronchitis, particularly if hospitalised with a

Interventional therapies Lung volume reduction surgery • Bullectomy • Bronchoscopic interventions with valves/coils/ablation • Transplantation •

Table 1

Table 1. NRT – nicotine replacement therapy, SABA – short-acting beta2 agonist, SAMA – short-acting anti-muscarinic, LAMA – long-acting muscarinic antagonist, LABA – long-acting beta2-agonist, ICS – inhaled corticosteroid, PDE 4 – phosphodiesterase 4, LTOT – long term oxygen therapy, NIV – non-invasive ventilation

Table 1. NRT – nicotine replacement therapy, SABA – short-acting beta2 agonist, SAMA – HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024 short-acting anti-muscarinic, LAMA – long-acting muscarinic antagonist, LABA – long-acting

Respiratory - COPD

20 Figure 2: Initial Pharmacological Treatment

Figure 2: Initial Pharmacological Treatment

COPD exacerbation in the past year. Roflumilast is not approved for reimbursement under the community drug schemes in Ireland.

bronchoscopic interventions may offer benefits. Palliative approaches are effective in managing symptoms for individuals with advanced COPD.

Long-term oxygen therapy (LTOT) is recommended for patients with severe resting chronic hypoxemia, i.e. PaO2 ≤ 7.3kPa or PaO2 ≥ 7.3kPa to ≤ 8.0kPa with pulmonary hypertension, pedal oedema or raised haematocrit. Its routine prescription is not advised for stable COPD with moderate desaturation, emphasizing the need for individualised evaluation. Long-term non-invasive ventilation (NIV) may reduce mortality and prevent re-hospitalisation in patients with severe chronic hypercapnia and a history of acute respiratory failure. For select patients with advanced emphysema unresponsive to medical care, surgical or

Role of Integrated Care in COPD management The population of Ireland is aging. People are living longer with increased levels of chronic disease. Often people with chronic disease access healthcare in a reactive, episodic manner, resulting in recurrent hospital admissions. Health services are now evolving to meet these changing population needs, with a paradigm shift away from hospital-centred care to person centred care. Integrated care for chronic disease, including COPD, is healthcare provided at the lowest level of complexity to meet patient needs. Patients are empowered to optimise their

chronic condition and to minimise risk factors. The National Clinical Programme (NCP) for Respiratory medicine, along with NCP Diabetes and NCP Heart Failure, form the main components of the Integrated Care Programme for Chronic Disease (ICPCD). The NCP Respiratory vision is for an end-to-end patientcentred integrated approach for persons living with COPD and asthma. COPD is included in the structured chronic disease treatment programme in primary care. Patients with COPD who have a medical card or GP visit card can avail of two free GP reviews in every 12-month period. A personalised care plan for patients with COPD is agreed between the patient and their GP or practice nurse, outlining steps to take to manage COPD and the supports available. An essential component of the Model of Care for

COPD is early detection of disease and diagnosis, whereby GP’s have direct access to spirometry. Integrated Respiratory Services, tailored to the individual needs of the patient, include COPD Outreach, Nurse-led clinics, Physiotherapy-led clinics, multidisciplinary team meetings to optimise management of patients with COPD, community-based pulmonary rehabilitation, oxygen clinics and Consultant-led clinics. The Integrated Respiratory Consultants provide a continuum of care across acute hospitals and specialist integrated care hubs. The Integrated Model of Care for COPD is very much aligned with the Sláintecare vision of the ‘Right Care, Right Place, and Right Time’. This new exciting way of working is optimising COPD patient care in Ireland, shifting care away from acute hospitals.

Respiratory News ERS Calls for Early-Career Member Award 2024 The European Respiratory Society (ERS) has announced that ERS members can now apply or nominate fellow members for the ERS EarlyCareer Members Award. The Early-Career Members Award is presented annually to a promising early-career member based on their potential for future

scientific contribution as well as past and current engagement in the Society. Early-career members (ECMs) are those members of the Society who are below the age of 40. This award is one of several ways that ERS shines a light on ECMs, who make up 33% of the overall ERS membership.

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Discussing the significance of the ECM Award, ERS President Monika Gappa noted, “ERS recognises the importance of its early-career members (ECM) and all that they contribute. The ECM Award honours the work of these members and acknowledges the potential for further contributions. This award reaffirms ERS’s

commitment to nurturing and supporting the future leaders of the respiratory field.” All ERS members are eligible to nominate a fellow member below the age of 40. ECMs can also put themselves forward for this award by applying. The deadline in both cases is 23:59 on 8 February, 2024.

KEYTRUDA for advanced gastrointestinal cancers KEYTRUDA (Pembrolizumab) is approved for the treatment of:1 COLORECTAL CANCER

In combination with trastuzumab + chemotherapy, is indicated for 1L treatment of locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinomas in adults whose tumours express PD-L1 with a CPS ≥ 1.

KEYTRUDA® (pembrolizumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION KEYTRUDA 25 mg/mL: One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. INDICATIONS KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic NSCLC in adults whose tumours express PD-L1 with a ≥1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD L1 with a combined positive score (CPS) ≥ 10. KEYTRUDA as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic HNSCC in adults whose tumours express PD-L1 with a ≥ 50% TPS and progressing on or after platinum-containing chemotherapy. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma (RCC) in adults. KEYTRUDA, in combination with lenvatinib, is indicated for the first line treatment of advanced renal cell carcinoma in adults. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers Colorectal cancer (CRC) KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first line treatment of metastatic colorectal cancer - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine based combination therapy. Non-colorectal cancers KEYTRUDA as monotherapy is indicated for the treatment of the following MSI H or dMMR tumours in adults with (a) advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation, (b) unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. KEYTRUDA, in combination with platinum and fluoropyrimidine based chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10. KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early stage triple negative breast cancer at high risk of recurrence. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple negative breast cancer in adults whose tumours express PD L1 with a CPS ≥ 10 and who have not received prior chemotherapy for metastatic disease. KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD L1 with a CPS ≥ 1. KEYTRUDA, in combination with trastuzumab, fluoropyrimidine and platinum-containing chemotherapy, is indicated for the first-line treatment of locally advanced unresectable or metastatic HER2-positive gastric or gastro-oesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1. DOSAGE AND ADMINISTRATION See SmPC for full details. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. KEYTRUDA must not be administered as an intravenous push or bolus injection. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Treat patients until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). For the adjuvant treatment of melanoma or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. Refer to the SmPC for dosing in neoadjuvant and adjuvant treatment of locally advanced, or early stage triple-negative breast cancer at high risk of recurrence. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued (a) For Grade 4 toxicity except for: endocrinopathies that are controlled with replacement hormones; or haematological toxicity, only in patients with cHL in which KEYTRUDA should be withheld until adverse reactions recover to Grade 0-1; (b) If corticosteroid dosing cannot be reduced to ≤10 mg prednisone or equivalent per day within 12 weeks; (c) If a treatment-related toxicity does not resolve to Grade 0 1 within 12 weeks after last dose of KEYTRUDA; (d) If any event occurs a second time at Grade ≥ 3 severity. Patients must be given the Patient Card and be informed about the risks of KEYTRUDA. Special populations Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment needed for mild or moderate renal impairment. No studies in severe renal impairment. Hepatic impairment: No dose adjustment needed for mild or moderate hepatic impairment. No studies in severe hepatic impairment. Paediatric population: Safety and efficacy in children below 18 years of age not established except in paediatric patients with melanoma or cHL. CONTRAINDICATIONS Hypersensitivity to the active substance or to any excipients. PRECAUTIONS AND WARNINGS Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Immune-mediated adverse reactions Immu-

As monotherapy is indicated for adults with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer in the following settings: •

1L treatment of metastatic colorectal cancer

•

2L treatment of unresectable or metastatic colorectal cancer after previous chemotherapy.

ne-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune mediated adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune mediated adverse reactions have also occurred after the last dose of pembrolizumab. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Immune-mediated adverse reactions are immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated nephritis, immune-mediated endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), immune-mediated skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). Refer to SmPC for more information and management of immune-mediated adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-mediated adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-mediated and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, vitiligo, dry skin, eczema, alopecia, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: neutropenia, anaemia, thrombocytopenia, leukopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dizziness, dyspnoea, cough, diarrhoea, nausea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pyrexia, fatigue, asthenia, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dysgeusia, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dry skin, dermatitis acneiform, dermatitis, eczema, pain in extremity, arthritis, acute kidney injury, oedema, influenza-like illness, chills, blood creatinine increased, blood alkaline phosphatase increased, blood bilirubin increased, hypercalcaemia. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis, nephritis, influenza like illness, chills, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers EU/1/15/1024/002 Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: August 2023 © 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin, D18 X5K7 or from www.medicines.ie. II133 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. KEYTRUDA Summary of Product Characteristics, Available at www.medicines.ie. CPS = combined positive score, 1L = first-line treatment, 2L = second-line treatment.,

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.

Date of Preparation: October 2023

In combination with chemotherapy for 1L treatment of locally advanced unresectable or metastatic oesophageal carcinomas or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.

GASTRIC OR GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA

IE-KEY-00794

OESOPHAGEAL CARCINOMAS

Written by: Dr Laura Staunton MCh MB BCh BAO, Ms Rebecca Weedle MCh FRCSI (CTh), Mr Ronan Ryan MD FRCSI (CTh), Mr Vincent Young MD FRCSI (CTh) & Mr Gerard J. Fitzmaurice MSc FRCSI (CTh), Department of Cardiothoracic Surgery, St James’s Hospital, Dublin

Respiratory - RATS

Robotic-Assisted Thoracic Surgery (RATS) is the pinnacle of modern thoracic surgical practice and was introduced at St James’s Hospital in July 2022. RATS enables a surgeon to perform Robotic-Assisted Thoracic Surgery – Early Results complex surgery on the chest using a console to control a number of robotic arms, offering advantages over traditional minimally invasive surgical techniques. At St James’s we offer a of an Expanding Program comprehensive minimally invasive thoracic surgical program with a minimally invasive Written by: Dr Laura Staunton MCh MB BCh BAO, Ms Rebecca Weedle MCh FRCSI (CTh), approach undertaken in up to 70% of our lung cancer operations. Mr Ronan Ryan MD FRCSI (CTh), Mr Vincent Young MD FRCSI (CTh) & Mr Gerard J. Fitzmaurice MSc FRCSI (CTh), Department of Cardiothoracic Surgery, St James’s Hospital, Dublin

Following a year of robotic thoracic surgical procedures, we have reviewed the early Robotic-Assisted Thoracic outcomes of ourSurgery expanding program combined withvisualisation our enhanced recovery Patient and complication rates (28-45%). improved due to complication protocol. rate in the first year (RATS) is the pinnacle of modern Patients also experience shorter a 3-dimensional camera that of our robotic program were very thoracic surgical practice and waslength of stay, chest drain duration, post-operative complications, as well outcomes including chest drain duration and reduced provides an enhanced view with low, with the main complication introduced at St James’s Hospital post-operative pain. highly magnified images. There of prolonged air leak (18%), in July 2022. RATS enables a as our robotic training program were examined. is a 6-Hz motion filter and motion consistent with other centres. surgeon to perform complex surgery on the chest using a console to control a number of robotic arms, offering advantages over traditional minimally invasive surgical techniques. At St James’s we offer a comprehensive minimally invasive thoracic surgical program with a minimally invasive approach undertaken in up to 70% of our lung cancer operations.

scaling system, which absorbs and filters physiological tremor, as well as offering dominant and non-dominant hand equivalence. The surgical movement is filtered by the robot, ensuring greater accuracy and precision. This ensures enhanced surgical dissection and suturing, with the resultant reduced surgical complications including blood loss. This facilitates improved systematic lymphadenectomies assisting with more accurate staging for lung cancer patients. As is evident in our patient cohort, RATS results in a shorter length of hospitalisation, facilitating a faster overall recovery time with the ability to return to normal activity.

There were no mortalities in our patient cohort.

Literature reports a post-operative length of stay averaging 4 days Training for patients undergoing for robotic surgery can be a paradigm shift for surgeons, RATS procedures. Early results from the RAVAL (Robotic-assisted video-assisted who versus are a group used to learning new techniques and approaches, lobectomy for lung cancer) trial, as well as prospective studies,givenhave shown reduced that the surgeon sits at a beside the mortality, hospital stay and complication rates (28-45%). Patients console also un-scrubbed experience shorter patient controlling a number of robotic arms. The main robotic chest drain duration and reduced post-operative pain. platform in use worldwide is the da

Following a year of robotic thoracic surgical procedures, we have reviewed the early outcomes of our expanding program combined with our enhanced recovery protocol. Patient outcomes including length of stay, chest drain duration, postoperative complications, as well as our robotic training program were examined.

Vinci® robotic platform produced by Intuitive Surgical Inc. At St James’s Hospital we have a dual console system comprising the latest da Vinci® Xi operating system. Training followed a pre-defined pathway involving initial online training, followed by simulator training on the da Vinci® Xi console at St James’s Hospital over a period covering approximately 30 hours. Surgical case observations were then undertaken overseas in Paris and London with international experts. The second stage of the training pathway involved local on-site training, with the Intuitive Surgical representative, involving both surgeon and theatre staff. Mr Fitzmaurice was the first Irishtrained surgeon to undergo 2-days of live simulation training as part of

Over the course of the first year, we have performed 32 robotic-assisted thoracic surgical operations in a stepwise incremental approach. This enabled the safe introduction of a new surgical technique within the department with a focus on case selection and staff engagement. The operations performed included diagnostic lymph node dissection, RATS does not, however, come thymectomies, sub-lobar resections, pleural-based chest wall tumour resections, and without challenges. Those specific Literature reports a post-operative to robotic surgery include high anatomical lobectomies. The median age ofcapital ourexpenditure patient cohort was 65 years with equal length of stay averaging 4 days costs and for patients undergoing RATS initial longer operating times distribution of gender. Our results demonstrated median chest drain duration of 1 day with procedures. Early results from with a a steep learning curve the RAVAL (Robotic-assisted for the entire surgical team. a median post-operative length of stay of 2 days. Pain was well controlled with intercostal versus video-assisted lobectomy Video-assisted thoracic surgery for lung cancer) trial, as well as RATS surgery has a number RATS share similar nerve blocks, patient control analgesia, and (VATS) oralandanalgesia that included paracetamol and prospective studies, have shown advantages when compared complications, although with reduced mortality, hospital stay to traditional open or minimally reducedin rates for RATSpatients including Ibuprofen with the occasional addition of opioids select on discharge. invasive thoracic surgical lower rates of blood loss, infection techniques. First, there is Figure 1: Chest drain duration and post-operative length of stay following RATS surgery

and prolonged air leak. The

Figure 1: Chest drain duration and post-operative length of stay following RATS surgery

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Part of the Thoracic surgical team beside our da Vinci® Xi robotic platform

this pathway at The Royal College of Surgeons in Ireland, with this stage previously having to be undertaken overseas. Initial cases were then undertaken with a visiting European Thoracic Surgical proctor building from straightforward to more complex cases. A typical patient can safely follow a fast track recovery pathway when appropriate. For example, recently a 74-year-old gentleman with an early stage Adenocarcinoma underwent a robotic-assisted right lower lobectomy and systematic mediastinal lymph node dissection, had his chest drain removed the following morning, and was discharged home well with pain controlled on oral analgesia that evening on the first post-operative day. The enhanced visualisation offered by the robotic platform also allows precise dissection near high-risk structures, such as major blood vessels. We recently resected a metastatic melanoma deposit from the aortic arch in a 71-year-old gentleman, who was discharged home well 2 days later. What does the future hold for robotic surgery? At St James’s Hospital we perform approximately 55% of all curative-intent lung cancer surgery in Ireland. The robotic program is now well established and as our experience develops in robotic surgery, so too should the ability to perform more complex robotic operations. Due

to the enhanced 3-D video quality and precision offered by the da Vinci® Xi system, cases including centrally-located tumours, sleeve resections, bilobectomies, pneumonectomies and resection post-neoadjuvant treatment have all been successfully reported. This offers great potential benefit to patients undergoing thoracic oncological surgery at St James’s Hospital, particularly with the transition towards neoadjuvant treatment for lung cancer patients. Research remains a key tenet of our mission to optimise treatment for lung cancer patients in Ireland. We now have a lung cancer MD research doctor, Dr Laura Staunton, who is exploring the perioperative immune profile, tumour immune microenvironment and efficacy of immunotherapy in patient-derived organoids (PDOs) in Non-Small Cell Lung Cancer (NSCLC) patients. This research is integrated within the Cancer Liquid Biopsies Consortium (CLuB), a collaboration between Trinity College Dublin (TCD), Queens University Belfast (QUB) and NUI Galway (NUIG). A longitudinal biobank of blood and matched tumour tissue samples are collected from patients with resectable NSCLC at St James’s Hospital. Multiple components of liquid biopsies including Circulating Tumour Cells (CTCs), Circulating Tumour DNA (ct-DNA),

As part of our expanding robotic and minimally invasive program, we have also updated our enhanced recovery after thoracic surgery (ERATS) program. This involves a number of key components including prehabilitation, nutritional support, smoking cessation, avoidance of fasting with carbohydrate loading, regional anaesthesia techniques, early mobilisation, as well as minimally invasive surgery. It is a 360-degree patient-centred methylated DNA and exosomes journey with the sole aim to are currently analysed as well provide optimal patient outcomes as the development of matched in lung cancer care. It’s important PDOs. This MD project, performed to recognise that any successful through TCD, aims to research the program is only as good as perioperative immune response the individual parts. We are and its association with clinical exceptionally to have a PDOs will be used to measure the effect of immunotherapy, whichfortunate will inform optimal timing outcomes. This is essential for dedicated of immune therapy to current treatment standards of care multi-disciplinary for NSCLC patients. With the risk stratification and developing team of healthcare professionals recent approval of Pembrolizumab for neoadjuvant / adjuvant treatment in resectable NSCLC, effective immunotherapeutic this study is at the forefront of lung cancer research innovation. whoand are constantly striving to strategies to improve long term deliver world class lung cancer patient PDOs As part ofoutcomes. our expanding roboticwill andbe minimally invasive program, we have also updated our care to our patients. Our roboticused to measure the thoracic effect of enhanced recovery after surgery (ERATS) program. This involves a number of key assisted thoraciccessation, surgicalavoidance program immunotherapy, which will inform components including prehabilitation, nutritional support, smoking of is a welcome addition for our fasting with carbohydrate loading, regional anaesthesia techniques, early mobilisation, as optimal timing of immune therapy wellcurrent as minimally invasivestandards surgery. It isofa 360-degree patient-centred the sole patients to assist journey them inwith this to treatment aim tofor provide optimal patient outcomes cancer care. It’s important to recognise that journey. care NSCLC patients. With thein lungdifficult any successful program is only as good as the individual parts. We are exceptionally fortunate recent approval of Pembrolizumab to have a dedicated multi-disciplinary team of healthcare professionals who are constantly for neoadjuvant / adjuvant striving to deliver world class lung cancer care to our patients. Our robotic-assisted thoracic treatment in resectable NSCLC, surgical program is a welcome addition for our patients to assist them in this difficult journey. this study is at the forefront of lung The St. James’s Hospital Thoracic cancer research and innovation. Surgical multi-disciplinary team were Figure 3: The St. James’s Hospital Thoracic Surgical multi-disciplinary team were finalists at finalists at the recent Irish Healthcare the recent Irish Healthcare Centre Awards Centre Awards

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

Respiratory - Inhalers

Inhaler technique – the why and the how Written by Ruth Morrow, Respiratory Nurse Specialist, Asthma Society of Ireland

manual dexterity, manual strength and ability to co-ordinate the inhaler all having an influence on whether the patient can use the inhaler (Rogliani et al, 2017) Types of inhaled medication Basically, there are 5 ways to deliver inhaled medication – meter dose inhalers (MDIs), breath activated devices, soft mist inhalers (SMIs), ) dry powder devices (DPIs) and nebuliser. For the purpose of this article, aerosol devices, breath actuated devices, DPIs and the soft mist inhaler will be addressed. The technique for each group will be discussed later in the article.

Inhaled medications Inhaled medications are essential for treating and asthma and COPD amongst other respiratory conditions. The big advantage of using inhaled medication is that the drug targets the lungs directly to where it is needed with little systemic absorption thereby lowering the risk of side effects when compared with oral or intravenous administration. On the other hand, inhaled medication is not suitable for everyone particularly those with poor inspiratory effort, poor dexterity, learning difficulties or cognitive impairment. A systematic review of inhaler technique involving 54,354 adults and children with either asthma or COPD investigated the extent and prevalence of inhaler use (Sanchis et al, 2016). The review assessed the most common errors made by patients, the percentage demonstrating correct, acceptable or poor technique and thirdly the change in outcomes over time. The overall results demonstrated a prevalence of correct inhaler technique in 31% of adults and children, acceptable technique in 41% and poor technique in 31%. The most frequent errors reported were incorrect preparation of the device, errors in co-ordination, incorrect speed or depth of inspiration and not holding the breath after inhalation (Sanchis et al, 2016). In the same study, there were difficulties reported in firing the MDI and breathing from the chamber.

Each inhaled device has specific characteristics for its use and care and therefore can be confusing for patients on more than one different device. Every effort should be made to ensure that patients are prescribed the same device for all their inhaled medications. However, this may not be possible depending on the drugs required to be delivered. In recent times, this has proved easier as there has been a surge of inhaler devices to the market which can be used as combination therapies. Good inhaler technique is essential • to optimize drug deposition into the lungs • to manage treatment failure • to improve symptoms which may result in de-escalation of treatment • to prevent inappropriate escalation of treatment • to avoid local side effects eg dysphonia, oral candidiasis Poor inhaler technique is associated with poor asthma control, frequent emergency department and GP visits, increased admission to hospital, increase in the levels of morbidity and mortality, increase costs, and inappropriate escalation of treatment (Hamdan et al, 2013). In COPD, poor inhaler technique can lead to poorly controlled COPD. In a study by Rogliani et al (2017), it was demonstrated each device has its pros and cons with age, cognitive status, visual acuity,

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Inhaler dose vs delivered dose Drug deposition within the lungs is dependent on the size of the drug particles. Particle size of more than 5 microns are deposited in the mouth and oropharynx. Particles measuring 2-5 microns are deposited in the upper and central airways and particles less than 2 microns are deposited in the peripheral airways and alveoli (Education for Health, 2015) The drug dose stated on the label is not the dose that is delivered to the lungs. The nominal dose is the dose that is stated on the label. The emitted dose is the amount released from the mouthpiece and the fine particle dose is the amount of drug released that is 5 microns or less in diameter that is deposited in the lungs. Considerations when choosing a device… Several considerations need to be considered when deciding on the appropriate device for a patient. Experience and research have shown that involving the patient in choosing the device aids better adherence (Lenney et al, 2000). What the patient wants from their inhaler, the drug formulary, the range of devices, the range of therapies and the cost of the medication are all considerations which health professionals should consider. From the patient’s perspective, the medication needs to fit into their lifestyle, their ability to use the device and the presence of physical or sensory impairment all can impact on the patient’s ability or willingness to use the device.

The environmental impact of inhaled medication has become a concern for both patients and health care professionals. GINA (2023) addresses the issue in their most recent guidelines. Propellants in the current pMDIs have 25x global warming potential than DPIs. New propellants are currently in development and are awaiting approval (GINA, 2023). Inspiratory effort For the drug to be optimally delivered to the lungs, adequate inspiratory effort is required. This can be checked by using an in-check dial device (Figure 1) to ensure the patient has sufficient inspiratory effort for the drug to reach the airways. A minimum inspiratory effort of 30 litres/min is required for optimal deposition. Some devices require higher inspiratory effort. Poor inspiratory effort will result in poor control of symptoms and an increased risk of side effects as the drug is deposited in the mouth and oropharynx. Starting inhaled medication – a check list… • Inhaler should not be prescribed unless the patient has been shown how to use it • If the medication is to be repeated, inhaler technique should be reassessed • Demonstrate inhaler technique using placebo devices which are available from all pharmaceutical companies • Do not switch inhaler unless the patient’s technique has been reviewed and assessed • Advise patient re storage and maintenance of inhaler device • Does the inhaler suit the patient, their lifestyle and the environment Common errors in inhaler technique The errors with inhaler technique can be categorised as follows: errors with the device, errors with patient, and errors with the health professional (Price et al 2012). Cultural barriers also exist with inhaler use. In some population, the use of an inhaler is seen as improper or impolite and oral medications may be preferred (Griffiths et al, 2004).

Inhaler technique – Soft Mist Device This device requires loading and priming by the pharmacist prior to dispensing to the patient. For daily use the patient: 1. Holds the soft mist inhaler upright with the cap closed

Figure 1: In check dial inspiratory flow meter

2. Turn the base in the direction of the red arrows until the inhaler clicks 3. Open the cap 4. Breathe out fully away from the device and

Errors with the device include: • Incorrect preparation of the device • Poor inspiratory effort • Using different devices to deliver different drugs – where possible the devices should be the same • Poor dexterity – inhaler aid devices are available to assist patients with reduced dexterity • Poor co-ordination of actuation and inspiration Errors with the patient include: • Reduced dexterity which may affect the patient’s ability to actuate the device

devices - slow and steady for MDIs, breath actuated devices and soft mist devices and quick ad deep for DPIs.

device and the breath is held for 10 seconds). Spacer devices need to changed according to the manufacturer’s instructions.

Inhaler technique – Meter Dose Inhaler

Inhaler technique - Breath actuated devices

1. Remove the cap

1. Shake the inhaler

2. Shake the inhaler 3. Breathe out gently away from the device 4. Put the mouthpiece in the mouth and at the start of inspiration press the canister down 5. Breathe in steadily and deeply 6. Hold the breath for 10 seconds or as long as possible

• Learning difficulties or cognitive impairment

7. Wait a few seconds before repeating steps 2-6

• Inhaling too fast or too slow for the device

8. Replace the cap

• Inappropriate device for the patient’s lifestyle Errors with the health professional include: • Not explaining to the patient how to use the device • Not demonstrating the inhaler technique • Not checking inhaler technique at every opportunity • Inadequate assessment of the patient’s inspiratory effort to ensure the device is appropriate • Inadequate assessment of the patient’s ability to use the device correctly Evidence indicates that patients who express a preference for a particular device are more likely to use their inhaler correctly and are easier to teach correct inhaler technique (Lenney et al, 2000). Inhaler Technique Basically, there are 2 inhalation techniques for using inhaled

To increase the deposition of the drug in the lungs with the MDI, a spacer can be used. This will also make actuation of the device easier for the patient. Inhaler technique using a spacer device All spacers have static charge which attracts the medication to the spacer walls thus reducing the amount of medication available for deposition to the lungs. The static charge can be reduced by washing the spacer in warm soapy water, soaking it for a few minutes and letting the spacer to “dripdry”. This will last for 4 weeks and the spacer does not need to be washed more frequently unless the patient experiences a respiratory tract infection. Then it should be washed more frequently. Spacers can be large Volumatic (eg Volumatic™) or small volume (eg Aerochamber™ or Free Breath spacer™). Spacers can used by using either the multiple breath technique (tidal breathing for 5-6 breaths) or the single breath technique (a single breath is inhaled after actuation of the

2. Hold the inhaler upright and open the cap 3. Breathe out gently away from the device. Keep the inhaler upright 4. Put the mouthpiece in the mouth and close the lips and teeth around the mouthpiece taking care not to block the air holes on the top of the inhaler 5. Breathe in steadily through the mouthpiece and continue to inhaler when the medication is released 6. Hold the breath for about 10 seconds 7. After use hold the inhaler upright and close the cap 8. For a second dose, wait a few seconds before repeating steps 1-6. Inhaler technique – Dry Powder devices Each dry powder device (easyhaler, diskus, elipta, breezhaler, turbohaler, genuair) all have specific preparation prior to use. For the inhalation of the drug, the patient: 1. Breathes out fully away from the device 2. Puts the mouthpiece fully into the mouth closing the lips around the mouthpiece 3. Takes a breath in deeply and quickly 4. Holds the breath for 10 seconds 5. Repeats these steps if a second dose is required

5. Close lips around the mouthpiece without covering the air vents. 6. Point the inhaler to the back of the throat 7. While taking a slow deep breath through the mouth, press the dose release button and continue to breath for as long as possible 8. Hold breath for 10 seconds or for as long as possible Written instructions on inhaler technique are readily available for all inhalers which should be given to patients. Inhaler technique videos are available on www.asthma.ie or by sending a message to the Asthma Society of Ireland WhatsApp messaging service on 086 0590132. All inhalers have specific care and maintenance and patients need to be educated regarding this to ensure medication is delivered in its optimum state. Information regarding care and maintenance is provided by the manufacturers. Conclusion This article has reviewed the importance of assisting the patient in the appropriate choice of inhaler device to optimally manage their condition whilst considering the environmental impact. The concepts of inhaled medication and optimal inspiratory effort have been explored. Common errors in inhaler technique have been discussed. Finally, inhaler technique for MDI, breath actuated devices, soft mist inhalers and dry power devices has been addressed. Useful Resource: Scullion J., Fletcher M., 2016, Inhaler standards and competency document. UK Inhaler Group https:// www.ukinhalergroup.co.uk/uploads/ iYf51ixS/ukig-inhaler-standardsjanuary-2017.pdf

References available on request

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

Respiratory - News

New Research in Genetic Lung Condition AATD Boosting levels of a deficient protein has clear survival benefits for people with the genetic condition alpha-1 antitrypsin deficiency (AATD), according to new research led by RCSI University of Medicine and Health Sciences.

researchers examined health data from 615 patients with severe AATD and the lung condition emphysema, tracking their progress over a period of about 10 years by looking at patient registries in Ireland, Switzerland and Austria.

The findings underscore a call to make augmentation therapy accessible to patients with AATD in Ireland and more widely across Europe.

“We showed that by boosting this protein in people who are born with very little of it, it is possible to protect them against early death caused by lung disease,” says the study’s first author Dr Daniel Fraughen, from the Irish Centre for Genetic Lung Disease, based at RCSI’s Department of Medicine.

People with severe AATD are born with very low levels of a protective protein called alpha-1 antitrypsin, and they can develop serious lung and liver disease. Previous studies of augmentation therapy in AATD showed it can slow the rate of lung damage that leads to emphysema and COPD, but they did not show a long-term benefit on survival. A weakness of these studies was that they included patients with AATD who already had serious lung disease. The new study gathered a realword perspective from patients with severe AATD who were not as seriously ill to start with. The

The countries in the study were chosen carefully, he explains. “We looked at three countries where access to standard medical care is equal, but access to augmentation therapy is not. In Switzerland and Austria, augmentation therapy is reimbursed but in Ireland it is not,” says Dr Fraughen. “This situation allowed us to test the effects of augmentation therapy on lung function decline and mortality.” The research showed that the people with AATD in Switzerland

and Austria benefitted from a clear survival advantage due to augmentation therapy that people with AATD in Ireland do not.

generates further evidence of efficacy for the only specific treatment for the lung disease caused by this condition,” she said.

“This study provides real world evidence for a survival benefit to augmentation therapy for emphysema caused by severe alpha-1 antitrypsin deficiency. From the data we could see that augmentation with alpha-1 antitrypsin confers a clear survival benefit in this real-world setting,” says study co-author Dr Tomás Carroll, a Senior Lecturer at RCSI and Chief Scientist at the patient advocate organisation Alpha-1 Foundation Ireland.

The findings also point to the need for early detection of AATD and to include younger and healthier patients in studies of augmentation therapy, notes study senior coauthor Professor Gerry McElvaney, RCSI Professor of Medicine.

The study, which involved collaborators in the USA, Austria and Switzerland and was coauthored by Geraldine Kelly, CEO of Alpha-1 Foundation Ireland, now provides evidence to support reimbursement of augmentation therapy for patients in Ireland and more widely across Europe. “As this therapy is not currently reimbursed in Ireland or in several other European countries, this international collaboration

“Future studies of augmentation therapy should recruit younger patients with less severe lung disease, says Professor McElvaney. “We also show that a majority of people with AATD are being diagnosed too late, by which time severe lung disease has already occurred. Detecting people with severe AATD as early as possible and intervening before the establishment of lung disease should be the goal to improve survival. This may require newborn screening for AATD.” Funding from the US Alpha-1 Foundation enabled this international study to take place.

COPD Patient Forum Event From left, Alana Kiernan, COPD Outreach Nurse Specialist; Patricia Mc Laughlin, Advanced Nurse Practitioner, Respiratory; Dr Olga Mikulich, Respiratory Consultant; and Eimear Masterson, COPD Outreach Physiotherapist

Respiratory Team at LUH and Respiratory Integrated Care Team

Dr Bukhari, Respiratory Consultant at Letterkenny University Hospital The respiratory team at Letterkenny University Hospital hosted a COPD Patient forum on 16th November 2023 in the Mount Errigal Hotel, Letterkenny. Approximately 5,500 people currently live with the condition in Donegal. Over 170 people attended on the day and had the opportunity to meet with all of the respiratory team. A series of presentations were delivered on the day including a new initiative from Respiratory Integrated Care, the virtual ward. JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

(pembrolizumab) Infusion 25mg/ml

KEYTRUDA: helping to redefine overall survival expectations for more patients with mNSCLC1-4

PD-L1 <1% or unknown

PD-L1 1-49%

PD-L1 >50%

NONSQUAMOUS

√

1st line Combination** Therapy3

SQUAMOUS

√

1st line*** Monotherapy4

NON-SQUAMOUS AND SQUAMOUS

√

Line

Histology

1st line Combination* Therapy2

reactions have also occurred after the last dose of pembrolizumab. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Immune-mediated adverse reactions are immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated nephritis, immune-mediated endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), immune-mediated skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). Refer to SmPC for more information and management of immune-mediated adverse reactions. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT): Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with classical Hodgkin lymphoma undergoing allogeneic HSCT after previous exposure to pembrolizumab. Infusion-related reactions: Grades 1, 2, 3 or 4 infusion reactions including hypersensitivity and anaphylaxis, could be seen with pembrolizumab treatment. Refer to SmPC for more information and management of infusion-related reactions. Overdose: There is no information on overdose with pembrolizumab. In case of overdose, monitor closely for signs or symptoms of adverse reactions and treat appropriately. INTERACTIONS No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. No metabolic drug drug interactions are expected. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. Corticosteroids can be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. FERTILITY, PREGNANCY AND LACTATION Women of childbearing potential Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Pregnancy No data on use in pregnant women. Do not use during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Breast-feeding It is unknown whether pembrolizumab is secreted in human milk. A risk to newborns/ infants cannot be excluded. Fertility No clinical data available. SIDE EFFECTS Refer to SmPC for complete information on side effects. Pembrolizumab is most commonly associated with immune-mediated adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-mediated and infusion-related adverse reactions. When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Monotherapy: Very Common: anaemia, hypothyroidism, decreased appetite, headache, dyspnea, cough, abdominal pain, nausea, vomiting, constipation, musculoskeletal pain, arthralgia, asthenia, oedema, pyrexia, diarrhoea, pruritus, rash, fatigue. Common: pneumonia, thrombocytopenia, neutropenia, lymphopenia, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, hyperthyroidism, dizziness, dysgeusia, pneumonitis, colitis, dry mouth, hepatitis, severe skin reactions, vitiligo, dry skin, eczema, alopecia, dermatitis acneiform, erythema, dermatitis, myositis, pain in extremity, arthritis, influenza like illness, chills, AST and ALT increases, increase in blood alkaline phosphatase, hypercalcaemia, blood bilirubin increased, blood creatinine increased, infusion related reaction. In combination with chemotherapy: Very Common: neutropenia, anaemia, thrombocytopenia, leukopenia, hypothyroidism, hypokalaemia, decreased appetite, insomnia, neuropathy peripheral, headache, dizziness, dyspnoea, cough, diarrhoea, nausea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pyrexia, fatigue, asthenia, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dysgeusia, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dry skin, dermatitis acneiform, dermatitis, eczema, pain in extremity, arthritis, acute kidney injury, oedema, influenza-like illness, chills, blood creatinine increased, blood alkaline phosphatase increased, blood bilirubin increased, hypercalcaemia. In combination with axitinib or lenvatinib: Very Common: urinary tract infection, anaemia, hypothyroidism, decreased appetite, headache, dysgeusia, hypertension, dyspnoea, cough, diarrhoea, abdominal pain, nausea, vomiting, constipation, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pain in extremity, fatigue, asthenia, oedema, pyrexia, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased. Common: pneumonia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, infusion-related reaction, adrenal insufficiency, hyperthyroidism, thyroiditis, hyponatraemia, hypokalaemia, hypocalcaemia, insomnia, dizziness, neuropathy peripheral, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), pneumonitis, colitis, pancreatitis, gastritis, dry mouth, hepatitis, severe skin reactions, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, arthritis, nephritis, influenza like illness, chills, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. PACKAGE QUANTITIES KEYTRUDA 25 mg/mL: 4 mL of concentrate in a 10 mL Type I clear glass vial. Legal Category: POM. Marketing Authorisation numbers EU/1/15/1024/002 Marketing Authorisation holder Merck Sharp & Dohme B.V., Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of revision: August 2023 © 2023 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin, D18 X5K7 or from www.medicines.ie. II133 Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie. Adverse events should also be reported to MSD (Tel: 01-2998700) References 1. Keytruda Summary of Product Characteristics, August 2023, available at www.medicines.ie. 2. Gandhi L, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378:2078-2092. 3. Paz-Ares L, et al. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018;379:2040–2051. 4. Reck, M et al. Pembrolizumab versus chemotherapy for PDL1 positive-non-small cell lung cancer, N Eng J Med 2016, 375(19)1823-1833. ALK=anaplastic lymphoma kinase; EGFR=epidermal growth factor receptor; mNSCLC=metastatic non–small cell lung carcinoma; PDL1=programmed death ligand 1.

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.

IE-KEY-00792

Date of Preparation: October 2023

* KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous NSCLC in adults whose tumours have no EGFR or ALK positive mutations. ** KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous NSCLC in adults. *** KEYTRUDA, as monotherapy, is indicated for the first-line treatment of metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a≥ 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations.

Respiratory - Cystic Fibrosis

Cystic Fibrosis Care in Ireland compared with other European Countries Written by Philip Watt CEO CF Ireland and President of CF Europe

Cystic Fibrosis care services and treatments in Ireland have progressed steadily over the past decade, but with still much more to do. Cystic Fibrosis is a life-long recessive genetic condition for which there is still no cure. Ireland has among the highest rates of CF in the world with among the most severe manifestations – in large part shaped by the genotype profile of the CF population in Ireland. CF primarily impacts on the respiratory and digestive systems, but also impacts on other organs of the body. Rising care standards in CF care in Ireland have been shaped by access to new and innovative drug therapies; the work of the National Clinical Programme for CF; our expert doctors and their teams; the data and benchmarks provided by the Cystic Fibrosis Registry and of course the sustained advocacy by Cystic Fibrosis Ireland over 60 years.

“We are now in a position in Ireland to aspire to a higher level of care long enjoyed by some of our European Union neighbours, such as Belgium, France and Germany, rather than fighting for basic services and/or exposing the continued significant weaknesses and gaps in promised CF services”

Improved hospital infrastructure in Ireland, additional clinical staff and high quality research, especially over the past decade, has made a major contribution to the progress in CF services. However with this progress, CF care has also become significantly more complex. As predicted survival increases year on year, co-morbidities associated with growing older and CF related liver and kidney disease have emerged as more significant issues for an increasing number of our patient population.

CF, such as Orkambi and most recently Kaftrio. In paediatric care in particular there is a growing sense that while CF remains a life threatening disease, it can now be managed much more effectively. ‘Fire-fighting’ is now being replaced in large part with ‘fire prevention’ for many children and younger people. It is also important to emphasise that CF impacts on individuals differently and not all have being able to access or tolerate Kaftrio for example, especially those with rarer gene mutations.

Predicted survival rates of people with CF have been significantly boosted by the emergence of the new and innovative drug therapies that treat the underlying cause of

However these wonderful new drugs cannot undo the damage to organs that has already occurred. For example, almost 100 people with CF in Ireland have a double

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

lung transplant. Some now need a kidney or liver transplant. This cohort of patients were also most at risk from the recent COVID-19 pandemic. Further investment in post-transplant CF care in the Mater (MMUH) and other hospitals has commenced and this is to be welcomed but more needs to be done. Transplant services in general in Ireland are still recovering from the COVID-19 pandemic. Rather than fighting for basic services, we are now in a position in Ireland to aspire to the higher level of care long enjoyed by some of our European Union neighbours, such as Belgium, Netherlands, France and Germany. Much of the work of Cystic Fibrosis Ireland over the past decade has been to fight for the full implementation of agreed government policy to enable us to meet accepted European standards. In some aspects we are now among the leading CF care providers in Europe but still with much more to do. CF adult care in Ireland was given a significant boost in recent weeks as a result of green lights being given to the commencement of building of the long promised 20 bed inpatient unit in Beaumont Hospital and the new adult CF outpatient centre in Merlin Park Galway. CFI contributed ¤700,000 to the Galway Unit which will cost a total of ¤3.4m. CFI has also raised more than ¤1m for the Beaumont CF Unit, which will cost around ¤22m. We thank the hospitals and the HSE for providing the main capital funding for both of these important initiatives though delays have made these projects significantly more expensive. Over the past decade Ireland has made strides to catch up with our European neighbours in other areas of CF care. For example in 2011, after 20 years of lobbying, CF was finally added to the list of conditions identified through the Heel Prick Test. This means that treatment for CF mow commences from birth rather than waiting months of inaction because of the absence of an accurate diagnosis.

Other patient groups, such as Sickle Cell and Thalassemia Ireland have been advocating for many years for similar inclusion in new born screening. The new CF drug therapies are still not a cure and up to one quarter of people with CF in Ireland have presently no access to CFTR Modulator drugs such as Kaftrio. In this context it is welcome to see that a dossier has now been forwarded to the European Medicines Agency by Vertex which seeks to broaden the license for Kaftrio in Europe, including Ireland. In June 2023 I was elected as President of Cystic Fibrosis Europe

(CFE), the umbrella group for 39 patient groups across greater Europe. From my increased interaction with other EU countries it is clear that CF care in Ireland is now aspiring to be in the top tier of CF care. Some countries in eastern and southern Europe only have rudimentary CF services. Access to drug therapies such as Kaftrio remains an aspiration for such countries, However there are some recent shafts of light. For example, the decision by pharma company Vertex to provide Kaftrio free of charge to patients in Ukraine is to be warmly welcomed. CFE continues to urge the global expansion of these ground breaking drugs through marketing strategies that takes into account regional levels of poverty and GDP. Individual governments must also be held to account for poorer CF care facilities.

Around 2009, the national lung transplant centre in the Mater Hospital was still largely in its infancy and depended on support from the Freeman Hospital in Newcastle for the few CF lung transplants then undertaken in Ireland. The lung transplant programme is now well established in Ireland and there is very little reliance on UK hospitals. However resourcing remains an issue. Ireland continues to lag behind other Council of Europe Countries in respect of all organ donation and transplants. This deficit is likely through a combination of under-investment in some aspects of donation and transplant services, but is also related to our present and outdated opt-in form of organ donor consent, which is thankfully about to change. Ireland should aspire to be in the top 10 organ donor and transplant countries in Europe, rather than our present position (28th place).

There are some 600 people (all diseases) waiting for a lifesaving transplant in Ireland (heart, lung, kidney, liver, pancreas). In this context, it is very welcome that the soft opt-out organ donor consent enabling provisions in the Human Tissue Bill, passed through the Report Stage in the Dáil on the 8th Of November 2023. Barring any last minute glitches the Bill should be enacted early in the new year. Soft opt out organ donor consent is the default in the rest of Europe including Spain which consistently has the highest levels of transplanting organs per head of population. It should also be cautioned recent experience in Wales shows that its takes 2-3 years for this improved form of organ donor consent to be fully functional. In conclusion, much done, more to do. CFI marks our 60th year. We were formed on a dark November day in November 1963. Our 2 ‘guiding lights’, with

the support of many, are Anne O’Dwyer, our founder and Bridie Maguire our first CEO. Bridie, a former Person of the Year, sadly passed away in October 2023. She was an amazing woman who lost 2 children to CF before they reached the age of 2 years of age. The fact that parents like Bridie and Anne continued to fight for better CF services and to support those in desperate need, even after the death of their own children, is a testament to the members and spirit of Cystic Fibrosis Ireland. It has been the priviledge of my life to had the opportunity to serve the CF community in Ireland and to have met people like Anne and Bridie. The story of CFI is available on our website in the Book ‘For the Roses’ see news item on Bridie Maguire. An 11 minute documentary to celebrate the 60th year of CFI is available on you tube ‘Someday, CF will stand for Cure Found’.

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

30 Prostate Cancer

Metastatic Prostate Cancer - A Review of Current Treatment Options and Promising New Approaches Written by Philip Posdzich,1,* Christopher Darr,1 Thomas Hilser,2 Milan Wahl,1 Ken Herrmann,3 Boris Hadaschik,1 and Viktor Grünwald1,2 Department of Urology, University Hospital Essen, 45147 Essen, Germany

Department of Internal Medicine (Oncology), University Hospital Essen, 45147 Essen, Germany

Department of Nuclear Medicine, University Hospital Essen, 45147 Essen, Germany

Prostate cancer is the most common solid cancer in men worldwide. The number of estimated new prostate cancers in the US in 2022 was 268,490. The number of estimated deaths due to prostate cancer is 34,500.1 Surgery and radiotherapy are the mainstay of treatment in localized disease. Androgen-deprivationtherapy (ADT), androgen signaling inhibition (ARSI) and chemotherapy dominate the standard medical treatment in recurrent or metastatic disease. However, the majority of patients acquire castrationresistance, which is associated with a poor prognosis. The latest advancements in systemic treatments were the addition of Poly ADP-Ribose Polymerase Inhibitor (PARPi) and radio-ligand therapies (RLT) to the

armentarium. While check point inhibitors (CPI) have revolutionized anti-cancer treatment in many diseases they were less successful in prostate cancer. A major driver of this immune resistance is derived from the dominance of a non-inflamed “cold” tumor environment in prostate cancer.2 However, some activity has been noted for ipilimumab in men with mCRPC who were treated with at least one chemotherapy and had evidence of progression after the discontinuation of ADT,3 as well as for pembrolizumab in a subgroup Table 1 instable prostate of genetically cancer patients.4

CHAARTED criteria High Volume -

Novel concepts are needed to advance immunotherapies in prostate cancer. Sipuleucel-T indicated that T-cell-based therapies were clinically active in principle and have led to further clinical development. Bispecific T Cell engager is a novel promising anti-cancer treatment modality in non-inflamed cancers, such as prostate cancer. These compounds re-direct T-cells to the tumor environment by targeting a cancer-specific epitope, such as PSMA in prostate cancer, which is linked to a component of the T-cell receptor (TCR). This mechanism recruits T-cells to the tumor milieu

by binding to prostate cancer cells, which activates T-cells and enables immunologic anti-tumor response. In this article, we will give an overview of the current therapy standard in mHSPC and mCRPC, and introduce bispecific T-cell-engager as a new mechanism of action to overcome immune resistance.

Table 1 CHAARTED criteria Low Volume

At least 4 bone metastases High volume criteria not met Including at least 1 outside vertebral column or pelvis or visceral metastasis

Table 2

LATITUDE Criteria JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Table 2 LATITUDE Criteria

Methods A review of the Medline database through PubMed was conducted to identify pivotal trials of approved and contemporary medical treatments in prostate cancer. Guideline-recommended regimens were selected and the current EAU Guideline on prostate cancer served as a reference. CURRENT TREATMENT OPTIONS IN METASTATIC PROSTATE CANCER Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Prognostic Factors Several criteria have been established to estimate the prognosis of metastatic hormone-sensitive prostate cancer. Most common criteria are CHAARTED and LATITUDE criteria. These are summarized in Table 1 and Table 2. The occurrence of “de novo” metastatic hormone-sensitive disease at the time of initial diagnosis was identified as a poor prognostic factor. The median overall survival (OS) was 51.6 months in low volume disease (HR = 1.64; 95% CI 1.16–2.31) and 43.2 months in high volume disease (HR = 2.48, 95% CI 1.83– 3.36) compared to the reference group (prior local treatment/low volume disease HR = 1). These results differed substantially from those patients who had local therapy prior to the diagnosis of metastatic disease, i.e., metachronous metastatic prostate cancer. In this population, OS in low volume disease was 92.4 months (HR = 1) and 55.2 months in high volume disease (HR = 1.9, 95% CI 1.31–2.75.7 ADT ADT is the standard treatment approach in mHSPC patients and may consist of Luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists or bilateral orchiectomy. In previous decades, ADT resided as single modality, but this is not the standard of care

At least 4 bone metastases High volume Including at least 1 outside vertebral column or pelvis or visceral metastasis

Table 2

LATITUDE Criteria High Risk

31 Low Risk

At least 2 risk factors of: - At least 3 bone metastasis High risk criteria not met - Visceral metastasis - ISUP 4 or higher

Table 3 OS in mHSPC (SOC) anymore.

of ADT + AAP reported significant OS improvement (HR = 0.62, 95% CI 0.51–0.76; p < 0.001) when compared to ADT alone. Three year OS rates were: 66% in ADT + AAP vs. 49% in ADT + Placebo group.6 In summary, the combination therapy of ADT + AAP provided a significant survival benefit over ADT monotherapy.

Enzalutamide: A Competitive in the ADT alone group (HR = 0.72, Androgen Receptor Blocker 95% CI 0.59 to 0.89; p = 0.0018). Subgroups of patients with high The ENZAMET trial included and low volume disease achieved mHSPC patients (with distant Today, therapies that combine ADT different treatment effects. While metastases (M1)Key and ECOG with ARSI, chemotherapy, or both, Therapy Findings ADT + docetaxel vs. ADT achievedTrial Name score 0–2). 1125 men (588 yielded superior OS results. Single a superior OS of 51.2 vs. 34.4 with high volume disease, 537 agent ADT has limited value and (HR = 0.63, 95% CI 0.50 SWOG 99–16 Docetaxel/Estramustinemonths vs. Mitoxantrone 17.5 mo with low volume disease) were(Docetaxel remains an option in elderly, frail to 0.79; p < 0.001) in high volume 1:1 randomized to receive patients, only. disease, there was no benefit in enzalutamide + ADT or ADT patients with low volume disease Combination Therapies Abiraterone+ Prendisolone vs. Prednisolone + Placebo COU-AA-302 34.7 (AAP) vs. 30.2 m + standard nonsteroidal in longterm follow-up (HR = 1.04, antiandrogen drug (bicalutamide, 10 The advent of combination 95% CI 0.70 to 1.55; p = 0.86). nilutamide, flutamide). Overall therapies has intensified medical Enzalutamide vs. Placebo PREVAIL OS 32.4 (Enz survival favored ADT + As a result, OS in newly treatment and improved OS enzalutamide (HR = 0.67, 95% diagnosed metastatic hormoneprognosis in prostate cancer CI 0.52–0.86; p = 0.002) and 3 sensitive prostate cancer is patients with mHSPC. Different year OS rate were 80% in the superior for ADT + docetaxel components were added to the Enzalutamide group and 72% for than ADT alone, but that effect of ADT backbone. ADT alone. Regarding the volume chemotherapy is restricted to high An early set of treatment of disease, the proportion alive volume disease only. intensification trials tested the after 36 months was 0.82 (0.75 to ADT + Androgen Receptor combination of ADT + docetaxel. 0.87) in the control group vs. 0.90 Signaling Inhibitors (ARSI) There were two important trials, (0.84 to 0.93) in the Enzalutamide which investigated the combination group and low volume disease. In Abiraterone Acetate: of ADT and Docetaxel. high volume disease, proportion Selective Inhibitor of Steroid alive after 36 months was 0.64 17α-Hydroxylase (CYP17A1) The STAMPEDE trial included (0.58 to 0.70) in the control group patients with newly diagnosed M1 In this section, we will discuss the and 0.71 (0.64 to 0.76) in the or N+ disease, locally advanced impact of three different androgen Enzalutamide group. There was no disease (cT3, cT4, ISUP grade at receptor signaling inhibitors in statistically significant impact of least 4, PSA at least 40 ng/mL) and addition to ADT. volume of disease (p = 0.14).12 patients with relapse after local treatment (PSA at least 4 ng/mL or The STAMPEDE trial also Apalutamide: Inhibitor of the PSA doubling time under 6 months investigated the impact of Ligand-Binding Domain of the or PSA level over 20 ng/mL, M or Abiraterone Acetate (AA), a Androgen Receptor N relapse). In all, 689/724 (95%) selective inhibitor of the enzyme In the TITAN study, apalutamide of patients in the control arm and steroid 17α-hydroxylase + ADT (n = 525) was compared 347/362 patients in the Docetaxel (CYP17A1) and prednisone in to ADT + Placebo (n = 527) in arm had no previous treatment. addition to ADT. Inclusion criteria patients with mHSPC. A total A total of 1184 patients received were already mentioned above. of 94 of 525 patients in the the standard of care (ADT) and In all, 957 received ADT alone, Apalutamide group and 79 of 592 patients received ADT + 960 patients were treated with 527 in the placebo group had docetaxel. The median OS in the ADT and Abiratrone Acetate + previous treatment for localized ADT group was 43.1 months, the prednisone (AAP). There was a disease. The other patients were estimated 5-year OS was 37% (CI significant benefit in OS (HR = de novo metastasized. The study 34–41%). In contrast, the median 0.63, 95% CI 0.52 to 0.76; p < reported superior OS in favor OS in patients who received ADT 0.001) in patients who received for the combination arm (HR + Docetaxel was 59.1 months, the the combination therapy which = 0.67, 95% CI 0.51–0.89; p = estimated 5-year OS was 49% corresponded to 3-year OS rates 0.005). After 24 months, there (p = 0.003, HR = 0.81, 95% CI 83% vs. 76%. Metastatic status was an overall survival of 82.4% 0.69–0.95).9 at time of randomization had no in the Apalutamide group, but significant impact on treatment The second Important trial was only 73.5% OS in the Placebo effect (p = 0.37).11 called CHAARTED, which also group13 In the final analysis after investigated the impact of ADT + In the LATITUDE trial, ADT + 405 deaths, it was shown that docetaxel in patients with mHSPC Placebo (n = 597 pts.) was apalutamide decreased the risk of and ECOG performance score compared to ADT + AAP (n = death by 35% (HR = 0.65; 95% CI, 0–2. A distinction was made 602 pts.). Only patients with 0.53 to 0.79; p < 0.0001).14 between high volume and low high-risk newly diagnosed The results of these trials volume disease. In the overall metastatic disease, ISUP grade indicated that the combination patient population, OS was 57.6 > 4, at least three bone lesions or therapy of ADT and ARSI months in the ADT + docetaxel measurable visceral metastases group in contrast to 47.2 months were included. The combination improved OS in mHSPC patients

patients treated with ADT alone is 8 about 42 months. Firstline options in CRPC.

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32 Prostate Cancer than ADT alone. Both patient groups, high volume disease and low volume disease had a benefit from combination therapy.

between the triple and ADT + ARSI doublets available. Metastatic Castration Resistant Prostate Cancer (mCRPC)

Triple Combinations (ADT + ARSI + Docetaxel)

Firstline Treatment in mCRPC

In this section, triple combinations in the treatment of mHSPC will be discussed.

First-line treatment in men with mCRPC differ. Most trials explored the role of treatments after the failure of ADT alone.

Darolutamide is a competitive androgen receptor inhibitor and reported improved metastasis free survival and overall survival in non-metastatic CRPC patients. The principal activity paved the way for further testing in an earlier setting. The ARASENS trial investigated the combination of darolutamide + ADT + docetaxel (n = 651) compared to placebo + ADT + docetaxel (n = 655). The primary analysis at first data cutoff showed that the risk of death was reduced by 32.5% in the triple-therapy arm when compared to the ADT + docetaxel doublet.15

Docetaxel was reported to improve OS compared to Mitoxantrone in the SWOG 99–16 trial. Docetaxel/ Estramustine (every 3 weeks 60 mg/m2) was compared to Mitoxantrone and prednisone (every 3 weeks 12 mg/m2). Patients who received docetaxel had an overall survival of 17.5 months whereas patients who were treated with Mitoxantrone had an OS of only 15.6 months (p = 0.02; HR = 0.80; 95% CI 0.67–0.97). There was a significant difference in rPFS:6.3 months (Docetaxel) vs. 3.2 months (Mitoxantrone) (p < 0.001).17

Abiraterone. This trial will be mentioned in detail in section “Molecular Therapies”. Firstline options in CRPC are summarized in Table 3 Options after Pretreatment in mCRPC For mCRPC patients who have already been treated with docetaxel, there are some therapeutic options, which will be listed below. Cabazitaxel is a novel taxane with activity in docetaxel resistant CRPC. In the TROPIC 2013 trial, Cabazitaxel + prednisone showed a benefit in 2 year OS in comparison to mitoxantrone + prednisone (OS > 2 years in 15.9% (60/378) vs. 31/377 (8.2%). (odds ratio 2.11; 95% CI 1.33–3.33).20 The value of AAP in treatment of mHSPC has already been mentioned above. Additionally, in mCRPC it is a possible therapy option after docetaxel. In COU AA 301 study, AAP was compared to placebo/prednisone and led to an OS of 15.8 months in AAP group vs. 11.2 months in the placebo arm. (p < 0.0001, HR = 0.74, 95% CI: 0.64–0.86). Median rPFS was 5.6 months (5.6–6.5) in AAP group and 3.6 months (2.9–5.5) in control group (HR = 0.66, 0.58–0.76; p < 0·0001).21

OS in ALSYMPCA (Radium 223 vs. Placebo in previous or no previous docetaxel). OS in patients who received Radium 223 was 14.9 months vs. 11.3 months in placebo group (p = 0.002, HR = 0.61; 95% CI: 0.46–0.81) The most common hematologic AE in the Radium-223 group was anemia (187/600 pts.; 31%) whereas bone pain (300/600 pts.; 50%) and nausea (213/600 pts.; 36%) where most common nonhematologic AEs.23 In the CARD study, Cabazitaxel was compared to Abiraterone or Enzalutamide in patients with mCRPC who were treated with Doxetaxel and Abiraterone or Ezalutamide. In all, 255 patients were randomized in two groups: one group received Cabazitaxel (129 pts.), the other group received Abiraterone or Enzalutamide depending on which they had not received yet (126 pts.). The median overall survival was 13.6 months in the Cabazitaxel group and 11.0 months in the Abiraterone/Enzalutamide group (HR for death = 0.64; 95% CI, 0.46 to 0.89; p = 0.008). The median progression-free survival was 4.4 months in Cabazitaxel group vs. 2.7 months in the other group. (HR for progression or death =0.52; 95% CI, 0.40 to 0.68; p < 0.001). As a result, Cabazitaxel resulted in longer overall survival and progression-free survival.24

PEACE-1 is a complex study The efficacy of abiraterone and consisted of four arms. At acetate before chemotherapy was this point, only the combination shown in the placebo controlled therapy of ADT + docetaxel with COU-AA-302 trial. Patients who or without abiraterone acetate and received abiraterone acetate + prednisone (AAP) were considered prednisone had superior OS than for analyses. The median rPFS those in placebo + prednisone was prolonged by 2.5 years in group (34.7 vs. 30.3 months HR patients who received the AAP 0.81, p = 0.0033). There was also containing triplet (HR = 0.5, a significant improvement in rPFS 95% CI 0.40–0.62; p < 0.0001). favoring AAP (16.5 months vs. 8.3 Furthermore, there was a 25% Enzalutamide has been Table 1 months; p < 0.0001).18 Molecular Therapy reduction in the risk of death in mentioned above. In the AFFIRM patients who received the triplet PREVAIL investigated trial, patients who received CHAARTED criteria The incorporation of molecular (HR = 0.75, 95% CI 0.59–0.95); p = the therapeutic benefit of enzalutamide after docetaxel had diagnostics deepened our 0.017). The addition of Abiraterone enzalutamide in comparison a significantly longer OS than understanding of putative High Volume Low Volume improved the median OS from to placebo in mCRPC in those who received placebo (OS therapeutic avenues in mCRPC. 4.72 years (SOC) to 5.72 years 18.4 vs. 13.6 months; (p < 0.001, At least 4chemotherapy-naïve bone metastases patients. BRCA 1 or 2 regulate homologous High volume criteria not met (SOC+abiraterone) (HR 1 = outside 0.82, vertebral Patients treated enzalutamide HR = 0.63; 95% CI: 0.53–0.75)). - Including at least column or with pelvis or visceral metastasis recombination (HR) and loss in 95% CI 0.69–0.98; p = 0.030). had an OS of 32.4 months There was also a statistically BRCA function may occur as Regarding compared to 30.2 months in significant difference in rPFS: 8.3 Table 2patients with high germline or sporadic alteration. tumor volume, there was a median placebo group (HR = 0.71, 95% months vs. 2.9 months (p < 0.001, BRCA deficient cancers are survival benefit of 1.5 years in CI 0.60–0.84, p < 0.001). rPFS HR = 0.63; 95% CI: 0.53–0.75) LATITUDE Criteria explicitly susceptible to PARP 22 patients who were treated with was significantly longer in patients that favored enzalutamide. inhibitors. The clinically most the triplet (HR = 0.72, 95% CI who received enzalutamide (20.0 High Risk Low Risk advanced PARP inhibitor in In patients with two or more 16 0.55–0.95; p = 0.019). months vs. 5.4 months (HR = mCRPC is olaparib. The PROfound symptomatic bone metastases At least 2 risk factors of: 0.186, 95% CI 0.15–0.23; p < study compared olaparib with As a result, triple therapies show and no visceral metastases, 19 0.0001). - At least 3 bone metastasis AAP or enzalutamide in patients a promising survival benefit in alpharadin (Radium 223) is also High risk criteria not met - Visceral with alterations in HR repair (HRR) mHSPC patients, metastasis especially in The PROPEL trial investigated a possible treatment option. or higher deficient CRPC after treatment those -withISUP high 4 tumor burden. the combination of Olaparib Besides symptom relief in bone There are no comparisons + Abiraterone vs. Placebo + metastases, it also led to a longer with a new hormonal agent. BRCA

Table 33 Table

Firstline options in CRPC

Firstline options in CRPC. Therapy

Docetaxel/Estramustine vs. Mitoxantrone

Trial Name SWOG 99–16

Key Findings 17.5 mo (Docetaxel) vs. 15.6 mo. (Mitoxantrone)

Abiraterone+ Prendisolone vs. Prednisolone + Placebo COU-AA-302 34.7 (AAP) vs. 30.2 months (Prednisolone + Placebo) Enzalutamide vs. Placebo

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

PREVAIL

OS 32.4 (Enzalutamide) vs. 30.2 mo

Statistics p = 0.02 HR = 0.80 p = 0.0033 HR = 0.81 p < 0.001

33 1 alteration was found in 8/256 pts in Olaparib group (3%) and 5/131 pts. in control group (4%). BRCA 2 alteration was found in 81/256 pts (32%) in the Olaparib group and 47/131 (36%) in the control group. In patients with at least one alteration in BRCA1, BRCA 2 or ATM, Olaparib achieved a superior rPFS (7.39 vs. 3.55 mo. (HR = 0.34; 95% CI: 0.25–0.47; p < 0.0001)) and OS (18.5 mo vs. 15.1 mo. hazard ratio for death = 0.64; 95% CI, 0.43 to 0.97; p = 0.02). In the overall population, the median OS at interim analysis was 17.5 months (Olaparib group) and 14.3 months (control group) (hazard ratio for death = 0.67; 95% CI, 0.49 to 0.93). Patients with BRCA alterations derived the largest benefit, which led to a restricted label in Europe. However, other HRR alterations seem to select for PARPisensitivity, but subgroups remain small and their predictive strength remains vague.25 In the PROpel study, 796 patients with mCRPC were randomized to receive Olaparib + Abiraterone (n = 399) vs. Placebo and Abiraterone (n = 397). In an interim analysis, rPFS was longer in Olaparib + Abiraterone group irrespective of HRR status (24.8 vs. 16.6 months; HR = 0.66, 95% confidence interval [CI] 0.54–0.81; p < 0.0001). Data on OS were immature at interim analysis.26 Based on these data, BRCA testing has entered the clinical routine in mCRPC. Alterations of the PI3 kinase/AKT signaling pathway are common in CRPC. PTEN is a suppressor of this signaling pathway and its loss is frequently found in CRPC. PTEN loss is associated with an aggressive clinical course and subject for pharmacological intervention in late stage mCRPC. Ipatasertib is an AKT inhibitor and its clinical efficacy was tested in a pivotal trial. Patients with previously untreated asymptomatic or mildly symptomatic mCRPC were eligible. The combination of Ipatasertib and AAP showed a benefit in rPFS in patients with PTEN loss in comparison to AAP + placebo (18.5 months vs. 16.5 months p = 0.0335, HR = 0.77, 95% CI: 0.61–0.98). There was no significant benefit on PFS in the intention to treat population (16.6 months (Placebo) vs. 19.2 months (HR = 0.84 [95% CI 0·71–0.99]; p = 0.043).27 A new therapeutic modality was introduced with the development of systemic PSMA-targeted radio

ligand therapy (RLT) in mCRPC. Lutetium-177-PSMA-617 (LUPSMA) is a small molecule that binds specifically to PSMA, which enables ß particle therapy to adjacent tumor cells in CRPC. A positive diagnostic 68-Gallium PSMA PET scan is a prerequisite to select suitable patients for this molecular therapy. The VISION trial tested LUPSMA in previously treated mCRPC patients who were not candidates for chemotherapy. LU-PSMA showed a significant benefit in rPFS (8.7 vs. 3.4 mo. (p < 0.001; HR = 0.40; 99.2% CI: 0.29–0.57)) and OS (15.3 vs. 11.3 mo. (p < 0.001; HR = 0.62; 95% CI: 0.5–0.74)) in comparison to standard of care (best supportive care, which consisted of hormonal therapy, denosumab, bisphosphonates, radiation therapy or glucocorticoids).28 Another important trial which proved the effectiveness of PSMA radioligand therapy was TheraP. It included previously treated mCRPC patients who were deemed fit for chemotherapy and patients were randomized to receive LU-PSMA or Cabazitaxel. Patient selection was more stringent and permitted only patients with a match of PSMAand FDG-PET activity. LU-PSMA RLT (up to six cycles; n = 98 pts.) was compared to Cabazitaxel (up to 10 cycles; n = 85 pts.). PSA response (defined as reduction of at least 50% from baseline), the primary endpoint, was shown in 66/98 (67%) pts who received PSMA RLT, but only 37/85 pts. (43%) who received Cabazitaxel (p < 0.001). Grade 3–4 adverse events occurred in 32 (33%) patients in the PSMA RLT group vs. 45 (53%) in the Cabazitaxel group. Overall, PSMA RLT showed improved efficacy and lower risk of grade 3–4 adverse events when compared to Cabazitaxel. However, the trial did not indicate major differences in OS in this trial and underlines the value of LUPSMA in direct comparison to Cabazitaxel in mCRPC patients, which is considered a life-prolonging therapy.29 Immunotherapy Until now, immunotherapy has not been of great importance in the treatment of prostate cancer and did not improve clinical outcomes significantly. Current trials test the role of ICI in specific subgroups: KEYNOTE- 641 is a Phase 3, randomized, double-blind, placebo-controlled trial, which investigates Pembrolizumab/

Placebo in combination with Enzalutamide in mCRPC patients who were not treated with abiraterone or progressed on Abiraterone and did not receive chemotherapy.30 Keynote-921 is a Phase 3, randomized, double-blind, placebo-controlled trial which investigates pembrolizumab/placebo in combination with docetaxel and prednisone in mCRPC patients who have received novel hormonal agents but no chemotherapy before.31 On 3 August 2022, the sponsor announced that the study did not meet its primary endpoints (improvement in overall survival and rPFS). KEYNOTE-991 is a Phase 3 trial to investigate the role of Pembrolizumab in combination with Enzalutamide and ADT versus Placebo in combination with Enzalutamide and ADT in mCRPC patients who did not receive novel hormonal agents before. The results of these trials are not available until 2025/2026 and could reform the rule of immunotherapy in prostate cancer.32 Keynote-365 is a multicohort phase Ib/II study which tests pembrolizumab in combination with Olaparib (Cohort A), Docetaxel and Prednisone (Cohort B), Enzalutamide (Cohort C). In the results published so far, PSA response was reported in 9% of patients in cohort A, 28% in cohort B and 22% in cohort C. The final results of this study are not yet available.33 Cell Based Immunotherapy So far, cell based immunotherapy has not found its place in the treatment landscape of mCRPC. This could change in the future due to ongoing developments. A therapy approach which was developed several years ago is supileucel-T. This is an active cell based autologous immunotherapy. Peripheral blood mononuclear cells are activated ex vivo with PA2024, a recombinant fusion protein of prostate antigen, which causes immune cell activation. Ultimately, mCRPC patients with an expected survival of at least 6 months received supileucel-T in a phase III trial (n = 341 pts.). In all, 171 patients received placebo as a control group. The OS in the supileucel-T group was 25.8 months and 21.7 months in the placebo group. (HR for death in the sipuleucel-T group = 0.78; 95% confidence interval [CI], 0.61 to 0.98; p = 0.03).34 Although showing principal activity, supileucel-T is not available in routine practice anymore.

Vaccination Vaccination against prostate cancer is not established in clinical practice. Nevertheless, there are studies that provided promising data. As an example, PROSTVAC, a PSA recombinant vaccinia vector, showed promising activity in mCRPC patients. Median OS was 8.5 months longer in pts who received PROSTVAC than in the control group (p = 0.0061).35 However, confirmatory trials were negative and did not show a benefit in OS.36 Bispecific T-Cell Engager The most advanced bispecific T-cell engager in the therapy of prostate cancer is PSMA Bite. PSMA is expressed in prostate cancer cells and metastases and can be used to specifically target therapies to prostate cancer cells, such as for LU-PSMA radioligand therapy.28 PSMA Bite is a new experimental treatment for mCRPC patients. PSMA Bite is a bispecific CD3 and PSMA antibody construct, which re-directs and activates T-cells to PSMA expressing cells. Bispecific T-cell engager (BiTE) is already established in the treatment of other malignancies. Blinatumumab was the first approved BITE therapy. It is a bispecific monoclonal antibody construct that causes CD3 positive T-cells to recognize and target CD 19 positive B-cells. Blinatumumab is approved for patients with refractory or relapsed precursor B-ALL. Compared to chemotherapy, blinatumumab showed a survival benefit in patients with pretreated B-ALL: Median OS in the blinatumomab group was 7.7 months compared to 4.0 months in the chemotherapy group (HR = 0.71; 95% CI 0.55 to 0.93; p = 0.01).37 Based on promising data from the treatment of hematological diseases, the suitability of bite molecules for the treatment of solid tumors is currently being investigated. A Phase I study of pasotuximab (PSMA Bite) tested its tolerability and activity in mCRPC. It included 68 patients in two cohorts of subcutaneous (s.c.) or intravenous (i.v.) application. These patients were pretreated with at least one taxane regimen and refractory to AAP or enzalutamide. Next, to evaluate the maximum tolerated dose in both cohorts, PSA response was investigated. In the subcutaneous cohort, every

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

34 Prostate Cancer patient developed anti-drug antibodies, which led to the premature discontinuation of the s.c. application cohort. PSA decline was −24.7% in pts. with s.c. treatment. In the i.v. group, median best PSA change was −22.0, −37.7 and −54.9% in 20, 40 and 80 µg/d dose cohorts. One patient in i.v. cohort had <50% PSA reduction for 50 weeks and stable disease for 337 days. Another patient in the i.v. cohort had nearly complete regression of lymphnode and bone metastases in PSMA-PET CT. PSA progression in long-term responders in i.v. cohort occurred after 11–17 months and indicates the principle

and dose-dependent activity of this new modality. Most common adverse events in both cohorts were fever (81% in s.c. and 94% in i.v. cohort), injection site reaction in the s.c. cohort (24/31; 77%), chills (23% in s.c. and 69% in the i.v. cohort) and fatigue (36% in the s.c. and 31% in the i.v. cohort). Treatment-emergend AEs occurred in both cohorts. Most common were anemia (39%) in the s.c. cohort and decreased lymphocyte count (44%) and infections (31%) in the i.v. cohort.38 Further trials to investigate the value and safety of PSMA Bite are ongoing. Other targets than PSMA may be used for bispecific T-cell engager,

such as Glypican-139 and ADAM 17 (disintegrin and metalloproteinase 17)40 or STEAP-1,41 which are under investigation. Overall, bispecific T-cell engager is a promising new therapy option with early signs of clinical activity. Of course, further clinical studies are necessary before they are ready for prime time, but early clinical trials are promising. Conclusions Prostate cancer is the most common solid cancer in men. In recent years, there have been major advances in the treatment of metastatic prostate cancer, which have pushed frontiers

of survival expectations to new levels. ADT alone is not enough anymore for men with metastatic HSPC. Men with BRCA 1/2 alterations and with PSMA-positive cancers benefit from targeted treatment with PARPi or Lu-PSMA, respectively. However, castration resistant prostate cancer remains a deadly disease and new therapies are needed. The advent of molecular therapies, such as RLT or PARPi, advanced the field more recently and early clinical trials indicate promising new therapeutic approaches, which includes immunotherapies. References available on request

News National Cancer Registry Annual Report The latest Annual Statistical Report from the National Cancer Registry (NCRI) focuses on the impact of age and stage at diagnosis on cancer outcomes. The report titled: Cancer in Ireland 1994 – 2021 is an analysis of nationally collated data revealing the status of cancer in Ireland including statistics on cancer incidence, mortality, and survival. Key findings include: • Early diagnosis is associated with better cancer outcomes, reduced complexity of care for patients and lower cost of cancer care. A high proportion of some cancers (e.g. melanoma, uterine and prostate cancers) present at early stage with consequent 5-year net survival of up to 100% in many cases. Cancers with a population screening programme also experience high 5-year net survival when detected in early stages. However, late presentation (stage IV) remains

common for some other cancers (e.g. head and neck, pancreatic and lung cancers) with consequent poorer outcomes. • Older people experience higher cancer incidence and lower survival rates compared to other age groups. 5-year net survival for those aged 75+ is 46%, compared with 86% for those in the 15 - 44 year age group. Internationally, it has been shown that many factors underlie these findings including delayed diagnosis as older people may present later for medical attention of symptoms, patients having other serious illnesses which limit treatment options, poorer treatment tolerance, reduced physiological reserve and lack of representation in clinical trials. • The number of invasive cancers (excluding non-melanoma skin cancers) presenting as an emergency was estimated at

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

14% during 2016-2019, down almost 6% since 2002. This fall from 20% to 14% was observed between 2002 and 2009, after which no further reduction was evident. Unfortunately, emergency presentation is associated with more advanced stage and therefore limited treatment options and poorer survival outcomes. • More complete data on the impact of the COVID-19 pandemic on cancer diagnoses in 2021 indicates that the pandemic resulted in a 4% reduction in cancer diagnoses compared to what was expected that year. Early indicators suggest a return to expected rates of cancer diagnoses in 2022. NCRI Director Professor Deirdre Murray said, “This year, the NCRI report emphasises some major themes that are core to planning for cancer control. Life expectancy

in Ireland is among the highest in Europe and we present the outcomes for cancer in older people, which will hopefully form a benchmark for policy makers and service planners in their work. Equally, we highlight the benefits of early diagnosis on cancer outcomes by cancer type and finally we report on cancers presenting as an emergency, both key indicators of cancer control.” Chair of the NCRI Board Dr Jerome Coffey, welcomed the report and added, “The Annual Statistical Report is the most important Registry output for everybody involved in organising and delivering cancer care. In addition to the key findings and themes listed above it is important to focus on the increase in total cancer cases over time, reflecting changes in the size and age profile of the population, and to ensure adequate healthcare capacity to meet this challenge.”

Hospital Professional

ONOURS 2024

Launching Soon! Hospital Professional Honours

Saturday, 14th September, 2024 Radisson Blu Hotel, Dublin For further information contact Aoife Hunter: aoife@ipn.ie

EVRENZO™ is like a breath of fresh air, in symptomatic EVRENZO mimics the body’s natural response to low oxygen conditions, such as those anaemia of CKD experienced at high altitude. By stimulating a coordinated erythropoietic response, 1

oral EVRENZO increases endogenous production of erythropoietin and improves iron bioavailability – ultimately leading to increased haemoglobin production and increased red blood cell production.1 All of which could reduce the complexity of current anaemia management.2

EVRENZO is indicated for treatment of adult patients with symptomatic anaemia associated with chronic kidney disease (CKD)1 Prescribing Information EVRENZO™▼ (roxadustat) film-coated tablets Name: EVRENZO 20 mg film-coated tablets, EVRENZO 50 mg film-coated tablets, EVRENZO 70 mg film-coated tablets, EVRENZO 100 mg film-coated tablets, EVRENZO 150 mg film-coated tablets. Presentation: Film-coated tablets containing 20 mg, 50 mg, 70 mg, 100 mg or 150 mg roxadustat. Indications: Treatment of adult patients with symptomatic anaemia associated with chronic kidney disease (CKD). Posology and Administration:Treatment should be initiated by a physician experienced in the management of anaemia. All other causes of anaemia should be evaluated prior to initiating therapy with EVRENZO and when increasing the dose. EVRENZO must be taken orally three times per week and not on consecutive days. The tablets are taken orally with/without food, swallowed whole and should not be chewed, broken or crushed. EVRENZO can be taken before or after dialysis (see SPC section 5.2). Individualise dose to achieve and maintain target haemoglobin (Hb) levels of 10–12 g/dL. Treatment should not continue beyond 24 weeks if a clinically meaningful increase in Hb levels is not achieved. Starting dose: Ensure adequate iron stores prior to initiation. Patients not currently/previously treated with an erythropoiesis-stimulating agent (ESA): Recommended starting dose: Patients <100kg: 70 mg three times weekly. Patients ≥100kg: 100mg three times weekly. Patients converting from an ESA: : Patients on ESA treatment can be converted to roxadustat. Dialysis patients stable on ESA: only consider conversion if clinically valid reasons exist. Non-dialysis patients stable on ESA: conversion not studied, only consider on benefit-risk to patient. The recommended starting dose is based on the average prescribed ESA dose in the 4 weeks before conversion. The first roxadustat dose should replace the next scheduled ESA dose. See Table 1. in the SPC. Maximum recommended dose: Patients not on dialysis do not exceed a roxadustat dose of 3 mg/kg body weight or 300 mg three times weekly, whichever is lower. Patients on dialysis do not exceed a roxadustat dose of 3 mg/kg body weight or 400 mg three times weekly, whichever is lower. Dose adjustments and Hb monitoring: The individualised maintenance dose ranges from 20 mg to 400 mg three times per week (400 mg only for CKD patients on dialysis). Monitor Hb every 2 weeks until a level of 10-12 g/dL is reached and stabilised, then every 4 weeks or as clinically indicated. The dose of roxadustat can be adjusted stepwise up or down from the starting dose 4 weeks after treatment start, then every 4 weeks except if the Hb increases by >2 g/dL, in which case the dose should be reduced by one step immediately. When adjusting the dose, consider the current Hb level and the recent rate of change in Hb level over the past 4 weeks, and follow the dose adjustment steps in Table 2 in SPC section 4.2. If dose reduction is required for a patient on the lowest dose, reduce the dose frequency to twice a week. If further dose reduction is needed, the frequency may be reduced to once weekly. Maintenance dose: After stabilisation of target Hb levels, monitor Hb levels regularly and follow dose adjustment rules. Consider alternative explanations in patients with inadequate Hb response (see SPC section 4.2). Patients starting dialysis while on roxadustat treatment: No specific dose adjustments required. Follow normal dose adjustment rules. Concomitant roxadustat treatment with inducers or inhibitors: When initiating/discontinuing concomitant treatment with strong inhibitors or inducers of CYP2C8, or inhibitors of UGT1A9, monitor Hb levels routinely and follow dose adjustment rules. Missed dose: If there is >1 day until the next dose, the missed dose must be taken as soon as possible. If ≤ one day remains before the next dose, skip the missed dose. Then resume the regular dosing schedule. Elderly: No adjustment of starting dose (see SPC section 5.2). Patients with hepatic impairment: Mild hepatic impairment: No adjustment of starting dose. Moderate hepatic impairment: Caution is recommended. Reduce starting dose by half or to the level closest to half the starting dose. Severe hepatic impairment: Not recommended (see SPC sections 4.4 & 5.2). Paediatric population: No data are available in patients < 18 years of age. Contraindications: EVRENZO is contraindicated in the following conditions: Hypersensitivity to the active substance, peanut, soya, or to any of the excipients listed in section 6.1 of the SPC; Third trimester of pregnancy (see sections 4.4 & 4.6 of the SPC); Breastfeeding (see section 4.6 of the SPC). Warnings and precautions: Cardiovascular and mortality risk: Overall, the cardiovascular and mortality risk for treatment with roxadustat has been estimated to be comparable to the cardiovascular and mortality risk for ESA therapy based on data from direct comparison of both therapies (see SPC section 5.1). Since, for patients with anaemia associated with CKD and not on dialysis, this risk could not be estimated with sufficient confidence versus placebo, a decision to treat these patients with roxadustat should be based on similar considerations that would be applied before treating with an ESA. Further, several contributing factors have been identified that may impose this risk, including treatment non responsiveness, and converting stable ESA treated dialysis patients (see SPC sections 4.2 and 5.1). In the case of non-responsiveness, treatment with roxadustat should not be continued beyond 24 weeks after the start of treatment (see SPC section 4.2). Conversion of dialysis patients otherwise stable on ESA treatment is only to be considered when there is a valid clinical reason (see SPC section 4.2). For stable ESA treated patients with anaemia associated with CKD and not on dialysis, this risk could not be estimated as these patients have not been studied. A decision to treat these patients with roxadustat should be based on a benefit risk consideration for the individual patient. Thrombotic vascular events: The reported risk of thrombotic vascular events (TVEs) should be carefully weighed against the benefits to be derived from treatment with roxadustat particularly in patients with pre existing risk factors for TVE, including obesity and prior history of TVEs (e.g., deep vein thrombosis [DVT] and pulmonary embolism [PE]). Deep vein thrombosis was reported as common and pulmonary embolism as uncommon amongst the patients in clinical studies. The majority of DVT and PE events were serious. Vascular access thrombosis (VAT) was reported as very common amongst the CKD patients on dialysis in clinical studies (see SPC section 4.8). In CKD patients on dialysis, rates of VAT in roxadustat treated patients were highest in the first 12 weeks following initiation of treatment, at Hb values more than 12 g/dL and in the setting of Hb rise of more than 2 g/dL over 4 weeks. It is recommended to monitor Hb levels and adjust the dose using the dose adjustment rules (see Table 2) to avoid Hb levels of more than 12 g/dL and Hb rise of more than 2 g/dL over 4 weeks. Patients with signs and symptoms of TVEs should be promptly evaluated and treated according to standard of care. The decision to interrupt or discontinue treatment should be based on a benefit risk consideration for the individual patient. Seizures: Seizures were reported as common amongst the patients in clinical studies receiving roxadustat (see SPC section 4.8). Roxadustat should be used with caution in patients with a history of seizures (convulsions or fits), epilepsy or medical conditions associated with a predisposition to seizure activity such as central nervous system (CNS) infections. The decision to interrupt or discontinue treatment should be based on a benefit risk consideration of the individual patient. Serious infections: The most commonly reported serious infections were pneumonia and urinary tract infections. Patients with signs and symptoms of an infection should be promptly evaluated and treated according to standard of care. Sepsis: Sepsis was one of the most commonly reported serious infections and included fatal events. Patients with signs and symptoms of sepsis (e.g., an infection that spreads throughout the body with low blood pressure and the potential for organ failure) should be promptly evaluated and treated according to standard of care. Secondary hypothyroidism: Cases of secondary hypothyroidism have been reported with the use of roxadustat (see SPC section 4.8). These reactions were reversible upon roxadustat withdrawal. Monitoring of thyroid function is recommended as clinically indicated. Inadequate response to therapy: Inadequate response to therapy with roxadustat should prompt a search for causative factors. Nutrient deficiencies should be corrected. Intercurrent infections, occult blood loss, haemolysis, severe aluminium toxicity, underlying haematologic diseases or bone marrow fibrosis may also compromise the erythropoietic response. A reticulocyte count should be considered as part of the evaluation. If typical causes of non-response are excluded, and the patient has reticulocytopenia, an examination of the bone marrow should be considered. In the absence of an addressable cause for an inadequate response to therapy, Evrenzo should not be continued beyond 24 weeks of therapy. Hepatic impairment: Caution is warranted when roxadustat is administered to patients with moderate hepatic impairment (Child Pugh class B). Evrenzo is not recommended for use in patients with severe hepatic impairment (Child Pugh class C) (see SPC section 5.2). Pregnancy and contraception: Roxadustat should not be initiated in women planning on becoming pregnant, during pregnancy or when anaemia associated with CKD is diagnosed during pregnancy. In such cases, alternative therapy should be started, if appropriate. If pregnancy occurs while roxadustat is being administered, treatment should be discontinued and alternative treatment started, if appropriate. Women of childbearing potential must use highly effective contraception during treatment and for at least one week after the last dose of EVRENZO (see SPC sections 4.3 and 4.6). Misuse: Misuse may lead to an excessive increase in packed cell volume. This may be associated with life threatening complications

of the cardiovascular system. Excipients: EVRENZO contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption should not take this medicinal product. EVRENZO contains Allura Red AC aluminium lake (see SPC section 6.1) which may cause allergic reactions. EVRENZO contains traces of soya lecithin. Patients who are allergic to peanut or soya, should not use this medicinal product. Effects on ability to drive and use machines: Roxadustat has minor influence on the ability to drive and use machines. Caution should be exercised when driving or using machines. Interactions: Effect of other medicinal products on roxadustat: Phosphate binders and other products containing multivalent cations: Roxadustat should be taken >1 hour after administration of phosphate binders or other medicinal products or supplements containing multivalent cations (not lanthanum carbonate) (see SPC section 4.2). Modifiers of CYP2C8 or UGT1A9 activity: Monitor Hb levels when initiating/ discontinuing concomitant treatment with gemfibrozil, probenecid, other strong inhibitors/inducers of CYP2C8 or other strong inhibitors of UGT1A9. Adjust the dose of roxadustat following dose adjustment rules based on Hb monitoring. (see SPC section 4.2). Effect of roxadustat on other medicinal products OATP1B1 or BCRP Substrates: Co administration of roxadustat with simvastatin in healthy subjects increased the AUC and Cmax of simvastatin and simvastatin acid. The concentrations of simvastatin and simvastatin acid also increased when simvastatin was administered 2 hours before or 4 or 10 hours after roxadustat. Co administration of roxadustat with rosuvastatin increased the AUC and Cmax of rosuvastatin. Co administration of 200 mg of roxadustat with atorvastatin increased the AUC and Cmax of atorvastatin. Interactions are also expected with other statins. Monitor for adverse reactions associated with statins and for the need of statin dose reduction. Roxadustat may increase the plasma exposure of other medicinal products that are substrates of BCRP or OATP1B1. Monitor for possible adverse reactions of co administered medicinal products and adjust dose accordingly. See SPC. Roxadustat and ESAs: It is not recommended to combine administration. Pregnancy and lactation: There are no data on the use of roxadustat in pregnant women. Roxadustat is contraindicated in the third trimester of pregnancy and is not recommended during the first and second trimester. If pregnancy occurs during EVRENZO treatment, discontinue EVRENZO and switch to an alternative if appropriate. EVRENZO is contraindicated during breast-feeding. Fertility: The potential effects of roxadustat on male fertility in humans are unknown. At a maternally toxic dose, increased embryonic loss was observed. Women of childbearing potential must use highly effective contraception during treatment and for at least one week after the last dose. Undesirable effects: Summary of the safety profile: The safety of EVRENZO was evaluated in 3542 non dialysis dependent (NDD) and 3353 dialysis dependent (DD) patients with anaemia and CKD who have received at least one dose of roxadustat. The most frequent (≥10%) adverse reactions associated with roxadustat are hypertension (13.9%), vascular access thrombosis (12.8%), diarrhoea (11.8%), peripheral oedema (11.7%), hyperkalaemia (10.9%) and nausea (10.2%). The most frequent (≥1%) serious adverse reactions associated with roxadustat were sepsis (3.4%), hyperkalaemia (2.5%), hypertension (1.4%) and deep vein thrombosis (1.2%). List of adverse reactions: Adverse reactions observed during clinical studies and/or in post-marketing experience are listed in this section by frequency category and MedDRA system organ class. Frequency categories are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). Infections and infestations: : Common: Sepsis. Endocrine disorders: Not known: Secondary hypothyroidism. Metabolism and nutrition disorders: Very common: Hyperkalaemia. Psychiatric disorders: Common: Insomnia. Nervous system disorders: Common: Seizures, headache. Vascular disorders: Very common: Hypertension, vascular access thrombosis (VAT)1, Common: Deep vein thrombosis (DVT). Gastrointestinal disorders: Very common: Nausea, diarrhoea, Common: Constipation, vomiting. Skin and subcutaneous tissue disorders: Not known: Dermatitis Exfoliative Generalised (DEG). Hepatobiliary disorders: Uncommon: Hyperbilirubinaemia. Respiratory, thoracic, mediastinal disorders: Uncommon: Pulmonary embolism. General disorders and administration site conditions: Very common: Peripheral oedema. Investigations: Not known: Blood thyroid stimulating hormone (TSH) decreased.1This adverse reaction is associated with CKD patients who were on dialysis while receiving roxadustat. Description of selected adverse reactions. Thrombotic vascular events: In CKD patients not on dialysis, DVT events were uncommon, occurring in 1.0% (0.6 patients with events per 100 patient years of exposure) in the roxadustat group, and 0.2% (0.2 patients with events per 100 patient years of exposure) in the placebo group. In CKD patients on dialysis, DVT events occurred in 1.3% (0.8 patients with events per 100 patient years of exposure) in the roxadustat group and 0.3% (0.1 patients with events per 100 patient years of exposure) in the ESA group (see SPC section 4.4). In CKD patients not on dialysis, pulmonary embolism was observed in 0.4% (0.2 patients with events per 100 patient years of exposure) in the roxadustat group, compared to 0.2% (0.1 patients with events per 100 patient years of exposure) in the placebo group. In CKD patients on dialysis, pulmonary embolism was observed in 0.6% (0.3 patients with events per 100 patient years of exposure) in the roxadustat group, compared to 0.5% (0.3 patients with events per 100 patient years of exposure) in the ESA group (see SPC section 4.4). In CKD patients on dialysis, vascular access thrombosis was observed in 12.8% (7.6 patients with events per 100 patient years of exposure) in the roxadustat group, compared to 10.2% (5.4 patients with events per 100 patient years of exposure) in the ESA group (see SPC section 4.4). Seizures: : In CKD patients not on dialysis, seizures occurred in 1.1% (0.6 patients with events per 100 patient years of exposure) in the roxadustat group, and 0.2% (0.2 patients with events per 100 patient years of exposure) in the placebo group (see SPC section 4.4). In CKD patients on dialysis, seizures occurred in 2.0% (1.2 patients with events per 100 patient years of exposure) in the roxadustat group, and 1.6% (0.8 patients with events per 100 patient years of exposure) in the ESA group (see SPC section 4.4). Sepsis: In CKD patients not on dialysis, sepsis was observed in 2.1% (1.3 patients with events per 100 patient years of exposure) in the roxadustat group, compared to 0.4% (0.3 patients with events per 100 patient years of exposure) in the placebo group. In patients on dialysis, sepsis was observed in 3.4% (2.0 patients with events per 100 patient years of exposure) in the roxadustat group, compared to 3.4% (1.8 patients with events per 100 patient years of exposure) in the ESA group (see SPC section 4.4). Skin reactions: : Dermatitis exfoliative generalised, part of severe cutaneous adverse reactions (SCARs), has been reported during postmarketing surveillance and has shown an association with roxadustat treatment (frequency not known). Prescribers should consult the full summary of product characteristics in relation to other adverse reactions. Overdose: Single supratherapeutic doses of roxadustat 5 mg/kg (up to 510 mg) in healthy subjects were associated with a transient increase in heart rate, an increased frequency of mild to moderate musculoskeletal pain, headaches, sinus tachycardia, and less commonly, low blood pressure (all non serious). Roxadustat overdose can elevate Hb levels above the desired level; manage with discontinuation or reduction of roxadustat dosage and careful monitoring and treatment as clinically indicated. Roxadustat and its metabolites are not significantly removed by haemodialysis. Package Quantities, Basic NHS cost: EVRENZO (12 pack tablets): United Kingdom (UK): 20 mg = £59.24, 50 mg = £148.11, 70 mg = £207.35, 100 mg = £296.21, 150 mg = £444.32. Ireland (IE): POA. Legal Classification: UK: POM. Ireland POM/S1A Product licence numbers: Great Britain (GB): PLGB 00166/0427-0431. Northern Ireland (NI)/ IE: EU/1/21/1574/001-005. Marketing Authorisation Holder: GB: Astellas Pharma Ltd., 300 Dashwood Lang Road, Bourne Business Park, Addlestone, United Kingdom, KT15 2NX. NI/IE: Astellas Pharma Europe B.V. Sylviusweg 62, 2333 BE Leiden, The Netherlands. Date of Preparation of Prescribing Information: February 2023. Document number: MAT-IE-EVZ-2023-00002 Further information available from: UK: Astellas Pharma Ltd., Medical Information: 0800 783 5018. IE: Astellas Pharma Co. Ltd., Tel.: +353 1 467 1555. For full prescribing information, please see the SPCs which may be found at: GB: www.medicines.org.uk; NI: https://www.emcmedicines. com/en-gb/northernireland/; IE: www.medicines.ie. United Kingdom Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/ yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Astellas Pharma Ltd. on 0800 783 5018. Ireland Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance, Website: www.hpra.ie or Astellas Pharma Co. Ltd. Tel: +353 1 467 1555, E-mail: irishdrugsafety@astellas.com.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. CKD, chronic kidney disease. 1.EVRENZO SMPC. 2. Sanghani NS, Haase VH. Adv Chronic Kidney Dis 2019; 26:253–266. MAT-IE-EVZ-2023-00007 | March 2023

CPD 104: CHRONIC KIDNEY DISEASE Continuing Professional Development

CPD

AUTHORS: Dr Colm Rowan, Specialist Registrar Nephrology, University Hospital Limerick Professor Austin Stack, Professor of Medicine, Consultant Nephrologist, University Hospital Limerick and School of Medicine, University of Limerick

60 Second Summary Chronic kidney disease (CKD) is a leading cause of morbidity and mortality affecting more than 1 in 10 adults globally. It is projected to become the fifth leading cause of death worldwide by 2040, a trend that mirrors the global rise in major CKD risk factors including diabetes, hypertension and obesity. Given the adverse outcomes associated with advancing CKD, early diagnosis of kidney disease is crucial and optimal control of risk factors is central to management and better patient outcomes. According to the Global Burden of Disease (GBD) study, the prevalence of CKD globally was estimated at 9.1% (8.5-9.8) of the world’s population in 2017. The global incidence of CKD has nearly doubled from 1990 to 2016. The prevalence of CKD in Ireland follows international trends. The National Kidney Surveillance System (NKDSS) [https://www. nkdss.ie/ ]reported a prevalence of 11.8 % (11.8-12.1) among adults aged 18 years and over in the health system, with this figure rising to 55.7% in patients over the age of 80 years. A diagnosis of CKD is associated with increased risk of morbidity and mortality. Several studies have found independent and inverse correlation between the level of kidney function and the risks of mortality. With progression of CKD, there is a progressive decline in kidney function with the development of several metabolic, nutritional, and volume-related complications including anaemia, hyperkalaemia, metabolic acidosis, mineral bone dysregulation, malnutrition, volume overload, and worsening hypertension. Ireland lacks a comprehensive national chronic disease surveillance system and thus the capability to generate robust estimates of disease burden, risk factors, levels of preventive care, and clinical outcomes. National health policy initiatives, Slaintecare and emerging Integrated Care Programmes for Chronic Disease have provided an important road map for improved coordination and delivery of chronic disease in Ireland.

Dr Colm Rowan

Professor Austin Stack

1. REFLECT - Before reading this module, consider the following: Will this clinical area be relevant to my practice?

knowledge gap - will this article satisfy those needs - or will more reading be required?

4 previous steps, log and record your findings.

2. IDENTIFY - If the answer is no, I may still be interested in the area but the article may not contribute towards my continuing professional development (CPD). If the answer is yes, I should identify any knowledge gaps in the clinical area.

4. EVALUATE - Did this article meet my learning needs - and how has my practise changed as a result?Have I identified further learning needs?

3. PLAN - If I have identified a

5. WHAT NEXT - At this time you may like to record your learning for future use or assessment. Follow the

Published by HPN. Copies can be downloaded from www.irishpharmacytraining.ie Disclaimer: All material published is copyright, no part of this can be used in any other publication without permission of the publishers and author. Astellas Pharma Inc. has no editorial oversight of the CPD programmes included in these modules.

Chronic Kidney Disease in the 21st Century New opportunities to stop a Silent disease Introduction Chronic kidney disease (CKD) is a leading cause of morbidity and mortality affecting more than 1 in 10 adults globally.1 It is projected to become the fifth leading cause of death worldwide by 2040, a trend that mirrors the global rise in major CKD risk factors including diabetes, hypertension and obesity.2 There is substantial variation in the prevalence of CKD internationally with large differences reported among ethnic minorities and across vulnerable socioeconomic groups.3-4 CKD is classified according to stage from 1 to 5, according to the level of kidney function, estimated using a mathematical equation (estimated glomerular filtration rate), with each increasing stage representing a worsening degree of kidney function.5 [Figure 1] The stage of CKD is further subclassified according to the presence or absence of albuminuria- the earliest sign of kidney damage. Patients with CKD experience substantial levels of morbidity and mortality compared to the general population.6 These risks develop at the earliest stages

of chronic kidney disease, and are present well before the onset of end-stage kidney disease (ESKD). Cardiovascular disease is the leading contributor to excess mortality in this population and the majority of patients succumb from sudden death rather than progress to kidney failure.6-7 The complexity of care increases enormously for patients with advancing stage of chronic kidney disease requiring the support of multidisciplinary clinical teams to manage complications and transition to renal replacement therapy.8

have translated scientific evidence into practical clinical guidelines for use in day-to-day practice. Professional bodies such as the Kidney Disease Improving Global Outcomes (KDIGO) group and the International Society of Nephrology (ISN) have provided clear guidance on the screening, diagnosis, treatment and monitoring of kidney disease with the goals of optimising disease management and ensuring effective implementation.13-16

Given the adverse outcomes associated with advancing CKD, early diagnosis of kidney disease is crucial and optimal control of risk factors is central to management and better patient outcomes.9 Over the past decade, there has been substantial scientific advancement in the diagnosis and treatment of CKD, which have laid the foundation for consolidated international guidelines and personalised treatment strategies.10-13 International organisations and societies primarily focused on the protection of kidney health and prevention of kidney disease

The global prevalence of chronic kidney disease has increased over the past three decades.17 According to the Global Burden of Disease (GBD) study, the prevalence of CKD globally was estimated at 9.1% (8.5-9.8) of the world’s population in 2017. The global incidence of CKD has nearly doubled from 1990 to 2016.17 A key driver of emergent trends is increased longevity and population growth. It is noteworthy that the incidence of CKD has been rising disproportionately in middle to low-income countries, largely as a result of increased burden of hypertension and diabetes.18 This

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The global landscape of CKD

38 CPD 104: CHRONIC KIDNEY DISEASE fication of CKD Based on GFR and Albuminuria Categories: Figure 1: Classification of CKD based on eGFR and Albuminuria Categories from the Kidney Disease: Improving Global Outcomes (KDIGO) Working Group. Heatmap representing the risk for CKD progression, all-cause death and cardiovascular death according to GFR and albuminuria categories.

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppls. 2013;3:1-150.

implies that the greatest burden of disease affects the most vulnerable with the least access to healthcare. Burden of CKD in Ireland The prevalence of CKD in Ireland follows international trends.19 The Survey of Lifestyle, Attitudes and Nutrition (SLÁN) study estimated the prevalence of CKD in Irish adults over 45 years old to be 11.6%.19 Data from the National Kidney Surveillance System (NKDSS) [https://www.nkdss.ie/ ] reported a prevalence of 11.8 % (11.8-12.1) among adults aged 18 years and over in the health system, with this figure rising to 55.7% in patients over the age of 80 years.3 The prevalence of CKD in the Irish health system is influenced by age, sex, acute kidney injury and location. A recent report from the Irish Longitudinal Study in Aging (TILDA) [https://tilda.tcd.ie/ publications/reports/]has provided further insight to CKD burden in older adults. Among this nationally representative cohort of community dwelling adults, the prevalence of CKD among adults aged 50 years or older was 11.7% in 2009-2011 and rose to 15.6% in 2014-2015. These data point to continued growth in CKD burden with

important implications for strategic planning and service provision. Impact of CKD on morbidity and mortality in Ireland A diagnosis of CKD is associated with increased risk of morbidity and mortality. Several studies have found independent and inverse correlation between the level of kidney function and the risks of mortality.6 Recent studies using Irish data from the NKDSS have quantified the impact of CKD on the rates and risks of hospitalisation and death. Compared to patients with preserved kidney function, the risks of hospitalisation were 5- fold higher for patients with severely impaired kidney function (kidney function less than 30% of normal) in Ireland.20 [Figure 2-3]. Similarly, death rates for patients with a diagnosis of severe kidney disease were between 10 to 20-fold higher compared to patients with preserved kidney function. These statistics suggest that substantial progress must be made to lessen the impact of CKD on disability. CKD-related complications With progression of CKD, there is a progressive decline in kidney function with the development

of several metabolic, nutritional, and volume-related complications including anaemia, hyperkalaemia, metabolic acidosis, mineral bone dysregulation, malnutrition, volume overload, and worsening hypertension.21-27 Cardiovascular disease (CVD) is the leading contributor to excess mortality in this population.23 Traditional risk factors for CVD are more common in CKD. Maladaptive neurohormonal mechanisms result in a greater incidence of hypertension. Moreover, alterations in cholesterol metabolism and pathogenic modifications of HDL/ LDL result in a pro-atherogenic environment. Non-traditional risk factors such as volume overload, a consequence of net sodium balance and a reduction in the functional nephron mass, can predispose to hypertension and progressive left ventricular hypertrophy. Accumulation of uraemic toxins is also contributory with the induction of inflammation and oxidative stress. Hyperphosphataemia, 1-25 Vitamin D deficiency and secondary hyperparathyroidism which characterise CKD-Mineral Bone Disease (CKD-MBD) also contribute to ectopic vascular calcification and atherogenesis.24

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However, CKD-MBD contributes to other pathologies such as renal osteodystrophy which predispose this population to fragility fractures. Anaemia frequently complicates advanced CKD . Several factors contribute to the anaemia of CKD including erythropoietin deficiency, iron deficiency and chronic inflammation.25 Studies reveal that anaemia has a major impact on a number of quality-of-life outcomes.26 Moreover, anaemia is yet another factor which heightens the risk of cardiovascular disease.27 Regional and national surveillance programmes can facilitate a better understanding of the burden of CKD and its associated complications on healthcare systems.28 CKD is silent for many patients Kidney disease is often asymptomatic for many patients in the early stages and there has been a growing interest in the development of national kidney surveillance programmes to enable early detection of disease and ensure effective implementation of treatment strategies to slow, delay or prevent kidney disease progression.3, 29-30 Early detection of kidney disease among highrisk groups and early deployment

Hospitalisation rates by level of kidney function in the hospitalisations increased x 5-fold 39 health system Rate per 100 Person years

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Figure 2. of interventions offer patients the greatest potential to prevent future kidney failure and extend patient survival. Moreover, socioeconomically deprived populations incur greater burden of CKD and are less likely to receive appropriate early intervention.31 Screening programs improve detection rates amongst economically deprived individuals and enhance access to care as a result. Early diagnosis and early treatment offer the opportunity to delay or prevent kidney disease progression and its complications, and stem the tide of kidney failure, which now stands at 2.5 million adults globally. The costs of renal replacement therapy-dialysis and transplantation are significant even for the wealthiest countries. In the Unites States, the costs of ESKD alone exceeds 114 billion dollars annually.32 Targeted Surveillance Programmes for CKD Ireland lacks a comprehensive national chronic disease surveillance system and thus the capability to generate robust

Stack et al European Renal Association May 2022 Stack et19 alTH European Renal Association estimates of disease burden, risk factors, levels of preventive care, and clinical outcomes.33-35 National health policy initiatives, Slaintecare and emerging Integrated Care Programmes for Chronic Disease have provided an important road map for improved coordination and delivery of chronic disease in Ireland. KDIGO has urged countries to invest in dedicated, comprehensive, and systematic surveillance programs designed to capture and track all aspects of CKD, in order to improve patients’ outcomes.36 In the United States, the Kidney Disease Surveillance System funded by the Center for Disease Control (CDC) is the first surveillance system of its kind to focus on tracking kidney disease prior to kidney failure and reduce the burden and impact of kidney disease.30 Programmes such as the Kidney Early Evaluation Program (KEEP) have also facilitated screen for high-risk individuals in the community.37 This program has been successful in detecting CKD in the early stages as well as generating knowledge about this condition to influence public health practices.

In Ireland, efforts are progressing at establishing a National Kidney Disease Surveillance System (NKDSS) to support early detection, treatment, and monitoring of kidney disease in the population. Pioneering work is under way to create the infrastructure to better understand kidney disease, its determinants and impact in the health system.3, 20, 28

Figure 2: Hospitalisation rates by level of kidney function in the Irish health system. 125, 890 patients were followed up for a median of 7.8 years and experienced 93, 515 hospitalisations in the period 2005-2013, mean age 54.1 years, 45% men, 55% women. eGFR (estimated glomerular filtration rate) ml/min/1.73m2 using CKD-EPI equation.

New Optimism for treating CKD in Ireland Over the past decade, several major scientific advances in the treatment of CKD have led to renewed optimism that CKD and its downstream consequences can be greatly attenuated and even prevented.38-40 The role of the rennin-angiotensin system as a maladaptive driver of CKD progression, proteinuria and fibrosis is well established.39-40 Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) have long been the cornerstone of CKD treatment by reducing proteinuria and optimising blood pressure control. The arrival of SGLT2 inhibitors have added another

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pillar of protection with major benefits in reducing the risk of CKD progression and extending patient survival by blocking glucose transport and promoting glycosuria.41-43 The non-steroidal selective mineralocorticoid receptor antagonist, finerenone has added a further dimension of protection by reducing disease progression in patients with Type 2 diabetes and albuminuria.44 The glucagon-like peptide 1 receptor agonist (GLP-1 Receptor) has also demonstrated significant benefits in kidney and cardiovascular protection in Type 2 diabetes.45 Together these treatments used in combination

Mortality ates by level rates of by kidney levelfunction of kidneyinfunction the Irishin the Irish system health system 104: CHRONIC KIDNEY DISEASE 40 CPDhealth Deaths per 1,000 person years

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Kidney Function (ml/min/1.72m Kidney2) Function (ml/min/1.72m2) Figure 3: Mortality rates by level of kidney function in the Irish health system. 125, 890 patients were followed up for a median of 7.8 years and experienced 14, 083 deaths in the period 2005-2013, mean age 54.1 years, 45% men, 55% women.

Browne et al :European Renal Browne Association et al :European 19TH May Renal 2022 Association 19

eGFR (estimated glomerular filtration rate) ml/min/1.73m2 using CKD-EPI equation.

have the potential to alter the course of CKD by preventing or delaying disease progression, reducing the need for dialysis, reducing cardiovascular events, and extending patient survival. A recent analysis suggests that that the gains in life expectancy, kidney and cardiovascular benefits were greatest for patients who were treated with a combination

of an SGLT2, GLP-1 RA, and non-steroidal MRA compared to renin-angiotensin system blockade alone.46 The global kidney community, and allied care partners recommend that each country develop a comprehensive CKD care strategy to effectively screen, diagnose and treat CKD. The roll-out

CPD Questions: Chronic Kidney Disease in the 21st Century New opportunities to stop a Silent disease 1. How common is chronic kidney disease globally?

of a national kidney disease surveillance programme would serve to assess the burden and population impact of CKD as well as evaluate the beneficial impact of traditional and novel preventive strategies. The Structured National Chronic Disease Management (CDM) programme of Slaintecare is already underway and represents a major step forward in public health

for managing chronic disease and multimorbidity. The addition of CKD to the CDM programme is the logical next step, providing a much needed opportunity for early detection and early treatment of disease with disease modifying and life extending therapies. References available on request

4. ACE inhibitors and ARBs are contraindicated in the treatment of chronic kidney disease! True or false? 5. What are the two most important screening tests for CKD in routine clinical practice?

2. How many stages are used to classify CKD in clinical practice? 3. Chronic kidney disease often presents with loin pain in older patients? True or false

6. List 3 pillars of treatment that are used to slow the progression of CKD in 2023?

Continued Professional Development supported by

BRING

PROTECTION TO LIFE1 GFR mL/min/1.73m2

INITIATE

treatment1,2

FORXIGA 10 mg Once daily

ABRIDGED PRESCRIBING INFORMATION

FORXIGA® (dapagliflozin) 5MG & 10MG FILM-COATED TABLETS.

Consult Summary of Product Characteristics (SmPC) before prescribing. Indications: Adults and children aged 10 years and above: Type 2 diabetes mellitus: For the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance, or in addition to other medicinal products for the treatment of type 2 diabetes. Adults: Heart Failure: Indicated in adults for the treatment of symptomatic chronic heart failure. Chronic kidney disease: Indicated in adults for the treatment of chronic kidney disease. Presentation: Film-coated tablets. 5mg or 10mg of dapagliflozin (as propanediol monohydrate). Each 5mg tablet contains 25mg of lactose. Each 10mg tablet contains 50mg of lactose. Dosage and Administration: Adults: Type 2 diabetes mellitus: The recommended dose is 10mg once daily. Consider a lower dose of insulin or insulin secretagogue such as a sulphonylurea when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Children and adolescents: No dose adjustment in children aged 10 years and above. No safety and efficacy data available for children below 10 years of age. Heart Failure: The recommended dose is 10mg once daily. Chronic kidney disease: The recommended dose is 10 mg once daily. Children and adolescents: <18 years: Safety and efficacy not yet established. Elderly: ≥65 years: No dose adjustment is recommended based on age. Renal impairment: No dose adjustment is required based on renal function. Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. If GFR falls below 45 mL/min, additional glucose lowering treatment should be considered in patients with diabetes mellitus if further glycaemic control is needed. Mild or moderate hepatic impairment: No dose adjustment. Severe hepatic impairment: Starting dose of 5mg is recommended, if well tolerated, dose may be increased to 10mg. Method of administration: Forxiga can be taken orally at any time of day with or without food. Tablets should be swallowed whole. Contraindications: Hypersensitivity to dapagliflozin, or excipients. Warnings and Precautions: Dapagliflozin should not be used in patients with type 1 diabetes mellitus. Renal impairment: Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. The glucose lowering efficacy of dapagliflozin is dependent on renal function, and is reduced in patients with GFR < 45 mL/min and is likely absent in patients with severe renal impairment. Hepatic impairment: Exposure is increased in patients with severe hepatic impairment. Use in patients at risk of volume depletion and/or hypotension: Dapagliflozin increases diuresis which may lead to a modest decrease in blood pressure, it may be more pronounced in patients with very high blood glucose concentrations. Exercise caution in patients for whom a dapagliflozin induced drop in blood pressure could pose a risk, such as patients on anti hypertensive therapy with a history of hypotension or elderly patients. Careful monitoring of volume status and electrolytes is recommended in conditions leading to volume depletion, such as acute gastrointestinal illness. In volume depleted patients temporary interruption of dapagliflozin is recommended until volume depletion is corrected. Diabetic ketoacidosis (DKA): Rare cases of DKA, including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including dapagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14mmol/L (250mg/dL). The risk of DKA must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, dapagliflozin treatment should be stopped immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with dapagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating dapagliflozin, factors in patient history that may predispose to ketoacidosis should be considered. Patients who may be at higher risk of DKA include patients with a low beta cell function reserve (e.g. patients with low C peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients. Restarting SGLT2 inhibitor treatment in patients experiencing a DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Dapagliflozin should not be used for treatment of patients with type 1 diabetes mellitus. Necrotising fasciitis of the perineum (Fournier’s gangrene): Postmarketing cases have been reported in female and male patients taking SGLT2 inhibitors. Urgent surgical intervention and antibiotic treatment is required. Advise patients to seek medical attention if they experience a combination of pain, tenderness, ©AstraZeneca 2022. All Rights Reserved. Veeva ID: IE-4836 Date of Prep: September 2023

No titration required except in patients with severe hepatic impairment1

erythema, or swelling in the genital or perineal area, with fever or malaise. Either uro-genital infection or perineal abscess may precede necrotising fasciitis. If suspected, discontinue Forxiga and institute prompt treatment (including antibiotics and surgical debridement). Urinary tract infections: Temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Elderly (≥65 years): No dose adjustment is recommended based on age. Elderly patients are more likely to have impaired renal function, be treated with medicines such as anti-hypertensives or diuretics, and be at a greater risk of volume depletion. Cardiac failure: Experience with dapagliflozin in NYHA class IV is limited. Infiltrative cardiomyopathy: Patients with infiltrative cardiomyopathy have not been studied. Chronic kidney disease: There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Patients with albuminuria may benefit more from treatment with dapagliflozin. Lower limb amputations: Counsel patients with diabetes on routine preventative foot care as an increase in cases of lower limb amputation (primarily of the toe) has been observed in long term, clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. Urine laboratory assessments: Patients will test positive for glucose in the urine due to mechanism of action. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Forxiga. Drug Interactions: Diuretics: Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues: Consider a lower dose of insulin or insulin secretagogue when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Interference with 1,5 AG assay: Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5 AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Alternative methods should be used. Interference with lithium: Dapagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after dapagliflozin initiation and dose changes. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium. Pregnancy and Lactation: Not recommended during the second and third trimesters of pregnancy. Treatment should be discontinued when pregnancy is detected. Do not use whilst breast-feeding. Ability to Drive and Use Machines: Alert patients on the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin. Undesirable Events: Consult SmPC for full list of side effects. Very common (≥1/10): Hypoglycaemia (when used with SU or insulin). Common (≥1/100 to <1/10): Vulvovaginitis, balanitis and related genital infections, urinary tract infection, dizziness, rash, back pain, dysuria, polyuria, haematocrit increased, creatinine renal clearance decreased during initial treatment, dyslipidaemia. Uncommon (≥1/1,000 to < 1/100): Fungal infection, volume depletion, thirst, constipation, dry mouth, nocturia, vulvovaginal pruritus, pruritus genital, blood creatinine increased during initial treatment, blood urea increased, weight decreased. Rare (≥ 1/10,000 to < 1/1,000): Diabetic ketoacidosis (when used in type 2 diabetes mellitus). Very Rare (< 1/10,000): Angioedema, necrotising fasciitis of the perineum (Fournier’s gangrene), Tubulointerstitial nephritis. Legal Category: Product subject to prescription which may be renewed (B). Marketing Authorisation Number: EU/1/12/795/002; EU/1/12/795/007. Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden. Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15. Tel: +353 1 609 71 00. FORXIGA is a trademark of the AstraZeneca group of companies. Date of API preparation: 02/2023 Veeva ID: IE-4664 References:

Adverse events should be reported directly to: HPRA Pharmacovigilance, Website: www.hpra.ie Adverse events should also be reported to AstraZeneca Patient Safety on Freephone 1800 800 899 1. FORXIGA 10 mg film-coated tablets. Summary of product characteristics. 2. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436–1446. eGFR = estimated glomerular filtration rate

42 Motor Neurone Disease

Current Management of Motor Neurone Disease Professor Orla Hardiman BSc MD FRCPI FTCD MRIA Consultant Neurologist, Beaumont Hospital, Professor of Neurology, Trinity College Dublin

Motor Neuron Disease (MND), also known as Amyotrophic Lateral Sclerosis (ALS) is characterized by combined upper and lower motor neuron degeneration with progression to death within 3 years. There is now compelling evidence to indicate that MND should be classified as a heterogenous neurodegenerative disorder that primarily affects upper and lower motor neurons (corticospinal and anterior horn cells) but that also involves other parts of the neuroaxis. There is now extensive evidence from clinical, imaging, pathology and genetic studies of extensive overlap between ALS and Frontotemporal dementia (FTD). Indeed, up to 70% of incident MND patients develop cognitive and behavioural impairment, with 13% of patients presenting with co-morbid behavioural variant FTD. The most common cognitive impairment presents as executive and language function, with relative preservation of spatial domains. Social cognitive and behavioural change is common, and apathy occurs in up to 70% of patients. There is no individual test that provides a definitive diagnosis of MND. All investigations are aimed at confirming the presence of upper and lower motor neuron degeneration, while excluding other conditions that could mimic the clinical presentation, such as motor neuropathies (e.g. multifocal motor neuropathy with conduction block), cervical myelopathy with polyradiculopathy, multiple sclerosis and other rare metabolic

conditions. Neuroimaging is performed to exclude structural pathology, and neurophysiological studies are performed to confirm the presence of acute and chronic denervation, the absence of sensory findings, and to ensure that mimic syndromes are excluded. A series of diagnostic criteria have established for ALS/MND – the most recently published being the Gold Coast Criteria, requiring progressive upper and lower motor neuron signs in at least region, and exclusion of other possible causes (BOX 1). However, there remains an urgent need for diagnostic biomarkers for MND. Candidate markers include neurofilaments which are elevated in CSF and blood in MND, altered levels of circulating microRNA, imaging and neurophysiology based technologies, although additional studies are required before these can be used in clinical practice. For most patients, definitive diagnosis takes 12 -15 months, and most patients are seen by 3-5 different healthcare professionals before the diagnosis is entertained. “Red Flags” that should alert the clinician to the possibility of MND include progressive painless loss of function in bulbar or limb regions, unexplained weight associated with dyspnoea, and the presence of progress dysarthria with associated tongue fasciculations. A number of initiatives to increase awareness have been launched, including a recent policy paper presented to the European parliament in September 2023 https://www. alscoalition.eu/.

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

In Ireland, the diagnosis and management of MND has been included as part of the HSE Modernised Care pathways https://www.hse.ie/eng/about/ who/strategic-programmesoffice-overview/modernised-carepathways/. The pathway provides a streamlined approach from first symptom of MND through to ongoing management integrated by the specialist multidisciplinary team at the national centre for ALS/MND in Beaumont Hospital, with outreach to community and palliative care services, and with extensive links to the Irish Motor Neuron Disease Association. Epidemiology The epidemiology of MND has been tracked in Ireland since 1994, using the Irish ALS/MND population based register. Ongoing surveillance has shown that the mean age of onset of MND is in the early 60s. Although the disease can occur throughout life, the peak age of onset is in the early 70s. There has been slight increase in both the mean and peak age of onset in the past 10 years, the reasons for which are not clear, but may related to the improving overall health of the population. The incidence in Ireland is also increasing, partly as a result of the ageing population. At present, there are approximately 140 new diagnoses every year. The prevalence in Ireland is 8.5/100,000, or approximately 450 people living with the condition. Based on data from the Irish ALS/ MND Register, we estimate that the overall lifetime risk in

Ireland for developing ALS is approximately 1:350. Genomics Population based studies have suggested that the development of the disease occurs in 6 steps, the first of which is genetic predisposition, and the remainder are probably environmental factors that have not been fully elucidated. MND is sometimes segregated into “familial” and “sporadic” subtypes of disease, although heritability studies indicate that genetic factors account for up to 51% of overall risk. These genetic factors include single genes of major effect, and/or a polygenic risk that most likely interacts with as yet unknown environmental factors. In Ireland around 15-10% of probands report a family history of MND or FTD, albeit with incomplete penetrance in the majority of kindreds. Within populations of European origin (Europe and USA) four genes account for up to 70% of all cases of “familial” ALS, namely C9orf72, TARDBP (coding for TDP43), SOD1 and FUS. In Ireland, the C9orf72 variant comprising a hexanucleotide repeat expansion, accounts for around 10% of all ALS, and 50% of the familial form of the disease. The prevalence of the remaining gene variants is extremely low. Disease penetrance in families is incomplete – most recent estimates for C9orf72-related MND are in the region of 20%. This low penetrance is in part explained by evolving evidence that the presence of the repeat expansion, although associated with disease, may a require addition factors for disease to manifest. Irish studies have shown that in families of those with the C9orf72 repeat expansion, the disease may also occur more frequently than expected in family members who do not carry the repeat expansion. Additionally, recent studies from the Irish ALS/MND group has found that cognitive performance of families carrying the C9orf72 variant differs from controls, regardless of the presence of the mutation. This suggest that unaffected family members carry additional factors that increase their risk of both cognitive change and an overall risk of developing MND. There is also evolving evidence of wider disease “endophenotypes” among family members of MND probands which is most likely genetically determined.

Higher rates of neuropsychiatric disease are reported in some kindreds of those with MND. These include an increased for psychosis and suicide among first degree relatives. This clustering is not related to the presence or absence of the C9orf72 repeat expansion. The observation of clustering of MND and neuropsychiatric conditions within some kindreds is important for two reasons. Firstly, the observation provides evidence that MND is heterogeneous, as the clustering is not uniformly distributed across all relatives of those with MND, but occurs more frequently among some kindreds. This heterogeneity may be a significant factor in the limited success in development of new therapeutics, as clinical trials to date have not accounted for different patterns of disease pathogenesis. Secondly, the presence of a family history of neuropsychiatric disorders is likely to reflect a subtype of MND with a specific set of genetic susceptibilities that are shared between ALS and psychiatric conditions . This hypothesis is supported by a combined genomewide association (GWAS) data from the international ALS/MND Consortium with data from the Psychiatric

Genome Consortium which has demonstrated a 14% polygenic overlap in the genetic basis of schizophrenia and MND . This suggests the presence of shared pathways of disruption within the brain. The association between MND and neuropsychiatric disorders supports the evolving evidence that both of these conditions can be considered as disorders of neural networking. While there already an extensive literature demonstrating that brain networking is disrupted in schizophrenia, the concept of MND as a "network disorder" is less well established, although evidence imaging and neurophysiologic studies is now compelling. Management and Treatment There is currently no effective treatment for MND, and management is symptom based through specialist multidisciplinary clinics. There is strong evidence that attending a specialist clinic improves survival, as patients have access to a multidisciplinary team that provides collective decision making, with multiple experts providing different perspective on the management strategy and care plan. Important interventions include management of weight loss with nutritional support, recognition and management of

declining respiratory function, with early introduction of non-invasive ventilation, and management of secretions. The specialist team also supports patients and their family in decision making around end of life, and provides both psychological and practical support to caregivers. Clinical Trials To date, Riluzole is only one licensed treatment for MND in Europe. While repeated studies have demonstrated that Riluzole is effective as a disease modifying agent, the effects are modest. Two additional drugs have been licensed for general use in the US and Canada, namely IV Edaravone and Albrioza. Additional Phase 3 trials have been required by the European regulatory agency. These are currently underway, and results will be available by mid-2024. Despite the urgent need for more effective treatments, clinical trials of over 100 other compounds in the past 15 years have failed to demonstrate efficacy, despite positive outcomes in animal models. The reasons for this failure in translation from animal models to human trials are multifactorial, but can be grouped into five major categories, namely: (1) disease heterogeneity, which also reflects our relatively limited knowledge

of the interplay between different disease mechanisms in humans; (2) use of pre-clinical experimental models to incorrectly infer how the disease is likely to develop in humans; (3) an absence of markers of pathogenic mechanisms, markers of disease onset, and quantitative markers of progression; (4) pharmacological challenges of dosing and measures of target engagement and (5) inefficient or poorly designed clinical trials. New approaches are now underway using better models that are more reflective of the human disease and to provide better biomarkers. New models include induced pluripotent stem cells from patients to explore the specific cell biological processes that are disrupted among affected cell types, and fly, zebrafish and rodent models that have been genetically modified using known human disease-causing variants. Targeted Gene Based Therapies Many of the recently identified genomic variants associated with MND encode RNA binding proteins (e.g TDP-43, FUS, ataxin-2) and stress induced secreted ribonucleases (e.g ANG). We know that a major pathological hallmark of MND is the mislocalisation of the RNA binding

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

44 Motor Neurone Disease protein TDP-43 from nucleus to cytoplasm. This occurs in 97% of patients with MND, leading to both loss and toxic gain-of function. TDP-43 is a regulator of gene expression through RNA splicing, DNA or RNA binding, and protein–protein interactions. It also plays a crucial role in several steps of RNA processing, including mRNA stability regulation, mRNA trafficking, pre-mRNA splicing, and regulation of non-coding RNA translation or function. The latter is thought to lead to cryptic splicing and polyadenylation of premessenger RNAs associated with altered RNA translation of several proteins, leading to random insertion of so-called ‘cryptic peptides’. Incorporation of cryptic exons and formation of aberrant proteins occurs downstream of TDP43 loss of function, including stathmin 2, which is required for axonal regeneration. Better understanding of these processes has led to exciting new therapeutic approaches using antisense oligonucleotides that target some of these disrupted pathways. Indeed, therapeutic initiatives using antisense oligonucleotides (ASOs) have now entered clinical trials. These include an anti-sense oligonucleotides (Tofersen) that targets inherited mutations in SOD1. Tofersen have recently been approved by the FDA as an effective treatment of SOD1 related MND. An ASO targeting mutations in the FUS gene (ION363) is currently in phase 1 trial, and additional ASOs in early phase trials include BIIB105 which targets ataxin 2 , and QRL-201, designed to restore the expression of the protein stathmin-2 by suppressing cryptic splicing. The success of the ASOs in treating some rare forms of MND demonstrates that value of a precision-medicine-based approach towards patient selection for specific treatment. As new and more targeted treatments are being developed, there is genuine optimism that MND may become a chronic rather than a fatal disease. These precision treatments are administered intrathecally by lumbar puncture, and are costly. But if successful they provide proof of principle that strategic targeting of known pathogenic pathways is a real therapeutic option. Notwithstanding, there also remains scope for development of other more conventional (small molecule) approaches toward treatment of MND for which there is no known associated gene variant. Despite the use of better models that can explore the cell biological processes that are disrupted in MND, there is also a need to expand the focus of research from laboratory-based

work and animal models to applied clinical research. Direct translation from animal models to humans does not fully take into account the greater complexity of the human nervous system, and individual aspects of a patient, including their genetic makeup, key biomarkers, prior treatment history, environmental factors and behavioural preferences, will all inform how human disease develops and progresses. This in turn influences design and testing of new treatments. Overcoming the factors that have limited the success of translational medicine requires novel solutions. Because MND is a rare disease, and likely comprises many different subtypes with different pathobiologic mechanisms, an important step is to develop a . system that enables collection and uploading of human data at a very

large scale, delivering a wealth of new multimodal, multi-sourced clinical phenotype and outcome, imaging, neuro-electric-signaling, biochemical and genomic datasets that will ultimately help to inform how we categorise each patient, and in turn, how we design and test new treatments using a plethora of new and emerging technologies. This is the objective of a novel international academic/ industry initiative. PRECISION ALS (www.precisionals.ie) is funded by Science Foundation Ireland, with participating clinical sites across the EU. The objective is to generated a large repository comprising multimodal data from over 6000 patients within the first 3-4 years, that will help to build a more extensive understanding of the different subtypes of disease, and that will provide well characterised patient

cohorts with particular attributes that can be enrolled rapidly in clinical trials. This is a large and complex task, and is mirrored by other initiatives in the US, including the Accelerated Medicine Programme for ALS (AMP-ALS) programme which will be funded by a partnership between the Foundation of the NIH and industry partners. (https://fnih.org/ourprograms/accelerating-medicinespartnership-amp/ ) Taking all of these initiatives together, there are grounds for considerable optimism that new and better targeted treatments will be available to those with MND in the future. And in the meantime, those living with the condition will continue to receive high quality evidence based care, with access to cutting edge clinical trials, as part of the HSE Modernised Care pathway for MND.

BOX 1 The Gold Coast criteria for the diagnosis of amyotrophic lateral sclerosis

Shefner JM, Al-Chalabi A, Baker MR, et al.. A proposal for new diagnostic criteria for ALS. Clin Neurophysiol 2020;131:1975–8. 10.1016/j.clinph.2020.04.005

1. Progressive motor impairment documented by history or repeated clinical assessment, preceded by normal motor function, AND 1. The presence of upper * and lower † motor neurone dysfunction in at least ONE body region ‡, with: • upper and lower motor neurone dysfunction noted in the same body region if only one region is involved, • or lower motor neurone dysfunction in at least TWO body regions, AND 1. Investigations§ excluding other disease processes.

*Upper motor neurone dysfunction implies at least one of the following: • Increased deep tendon reflexes, including the presence of a reflex in a clinically weak and wasted muscle, or spread to adjacent muscles. • Presence of pathological reflexes, including Hoffman sign, Babinski sign, crossed adductor reflex, or snout reflex. • Increase in velocity-dependent tone (spasticity). • Slowed, poorly coordinated voluntary movement, not attributable to weakness of lower motor neurone origin or Parkinsonian features. †Lower motor neurone dysfunction in a given muscle requires either : • Clinical examination evidence of muscle weakness and muscle wasting, or • EMG abnormalities that must include both: • Evidence of chronic neurogenic change, defined by large motor unit potentials of increased duration and/or increased amplitude (with polyphasia), and motor unit instability regarded as supportive but not obligatory evidence, and • Evidence of ongoing denervation, including fibrillation potentials or positive sharp waves, or fasciculation potentials. ‡Body regions are defined as bulbar, cervical, thoracic and lumbosacral. To be classified as an involved region with respect to lower motor neurone involvement, there must be abnormalities in TWO limb muscles innervated by different roots and nerves, or ONE bulbar muscle, or ONE thoracic muscle, either by clinical examination or by electromyography (EMG). §The appropriate investigations depend on the clinical presentation, and may include nerve conduction studies and needle EMG, MR or other imaging, biofluid studies, or other modalities as clinically indicated.

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Kidney Disease 45

Characterising Chronic Kidney Disease Findings from the largest study to date in Ireland to characterise the population affected by chronic kidney disease (CKD), over the age of 50 years, have been published. The research was undertaken in collaboration with the National Renal Office (Health Service Executive (HSE)) who also part funded this project. While valid attempts have been made to report the prevalence of CKD in Ireland, to date none have focused on a longitudinal cohort study based on a stratified random sample of the general population. Similarly, the incidence of CKD in the Irish general population has not been investigated to date and the Irish Longitudinal Study on Ageing (TILDA) provided the research team with the most suitable substrate in which to study this. The presence and severity of CKD identifies individuals who are at increased risk of adverse health outcomes, including cardiovascular disease, premature death, and potentially progression to requiring dialysis or a kidney transplant and premature mortality; and as such, preventing and managing CKD constitutes a key aim of overall management. Findings (based on TILDA data from 2009-2011 ‘Wave 1’ and 2013-2015 ‘Waves 2- 3’) CKD prevalence in adults aged 50 years and over in Ireland is rising. While this is likely to be primarily related to ageing and improved survival in the general population, these trends highlight the importance of continued public health action to raise awareness and to improve the care and outcomes for people with CKD. • CKD was present in 15.6% of people aged 50+ in Ireland, which equates to approximately 226,000 people or 1 in 7 of the population. • 98% of people who had CKD were unaware they suffered from it. • Whereas blood pressure management should be tightly controlled in CKD to prevent or slow down progression, blood pressure was poorly controlled in CKD in Ireland. • CKD is becoming more common over time in Ireland, consistent with Ireland’s rapid demographic changes, highlighting the

importance of action in primary and secondary care to raise awareness and to improve the outcomes for people living with CKD in Ireland. • New cases of CKD in Ireland in people aged 50+ are occurring at a rate of 16 people per 1000 person-years of follow up which will likely also contribute to substantial future demand on Nephrology services and hospital inpatient stay now and in future. • Hypertension was the most common CKD-related condition in the Irish adult population. The estimated prevalence of CKD in Irish adults aged 50+ years without diabetes and hypertension was 6.22 % based on Wave 1 data and 10.01% based on Wave 3 of TILDA. Age, blood pressure, HbA1c, BMI and hypertension were significantly associated with the presence and severity of CKD. The increasing prevalence of CKD has implications for future treatment policies in nephrology in Ireland, including healthcare resource allocation planning as part of Sláintecare as well as the implications of new treatment

options for CKD on the Chronic Disease Management Programs in Ireland.

SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists and GLP-1 analogues.

New treatments proven in trials to alter the course of CKD thereby reducing progression to established kidney disease, are now also available for patients.

 CKD should not be viewed in isolation, but as an integral part of the management of the other long term conditions that the majority of people with kidney disease have, such as diabetes, hypertension, heart failure and cardiovascular disease. In fact these comorbidities and conditions may be even more relevant to an individual’s current and future well-being since people with early stage CKD are much more likely to suffer premature death due to cardiovascular disease than to progress to end stage renal disease requiring dialysis or kidney transplantation.

Recommendations  This Report clearly identifies that although CKD is common in the general population of Ireland aged 50 years and over, most people are unaware that they have CKD. We advocate for increased public awareness campaigns since it is of paramount importance to highlight the significance of CKD in the general population. This is particularly the case in light of the risk of progression of CKD to more advanced stages, the associated cardiovascular disease and premature mortality risk, in addition to the risk of acute kidney injury and medication prescribing errors. Furthermore, contemporary treatment strategies have emerged to reduce the risk of progressive worsening of kidney function and cardiovascular risk such as the

 Our study suggests that 98% of TILDA participants with CKD aged 50 years and above were not aware of CKD. In addition the frequency of poorly controlled hypertension based on guideline treatment targets in patients with established organ damage in the form of CKD is alarming. The cardiovascular, cognitive and comorbidity implications of untreated hypertension in CKD could

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

A Report from TILDA and the National Renal Office.

46 Kidney Disease www.tilda.ie “The incorporation of chronic kidney disease into the chronic disease management program in Ireland may facilitate improved treatment of the condition in primary care” be highlighted and addressed by the inclusion of CKD in the primary care chronic disease management programme.  CKD has huge cost implications for healthcare, as was highlighted by the recent Kidney Research UK report which highlights CKD as a public health emergency. 1  The National Renal office (NRO) proposes to use the clinical epidemiology data from this report to inform the design of the model of care and service development for early CKD in the community and to advocate for CKD to be part of the National Chronic Disease Management Program Lead author Professor Donal Sexton of TILDA and Consultant Nephrologist at St James’s Hospital said, “This report is extremely important for people with chronic kidney disease living in Ireland since it highlights not only how common it is but also emphasises the public health requirement to improve awareness and treatment in the light of new approved medications. The incorporation of chronic kidney disease into the chronic disease management program in Ireland may facilitate improved treatment of the condition in primary care.” Professor Rose-Anne Kenny, Principal investigator of TILDA said, “Ireland is the fastest ageing country in Europe. In Ireland, we spend one fifth of our lives with disability and significant disease. CKD is an important and hitherto neglected cause of such disability in ageing. The aim of this TILDA research is to characterise CKD in adults in Ireland and raise awareness of how common it is (1 in 7 adults over 50y) and how, if it is identified sufficiently early, we can manage its course and lessen its more severe health

Chronic Kidney Disease in Ireland: Evidence from TILDA About Chronic Kidney Disease Chronic Kidney Disease (CKD) is linked to an increased risk of heart disease and premature death. Treating high blood pressure and other risk factors for kidney disease can protect kidney and heart health, and prevent the need for dialysis. Over the past 10 years, the number of patients treated by dialysis or kidney transplantation has increased by 30%. This costs the State almost €1 million per day to treat.

17 in

People with high blood pressure or diabetes are up to 3 times more likely to have CKD

More than people aged 50+ and over have CKD in Ireland (over 200,000 people)

Risk Factors About 50% of adults with CKD have uncontrolled blood pressure

Chronic Kidney Disease is common CKD is more common with increasing age and among women

Based on TILDA data collected from 2009-2011 and 2014-2015, CKD is rising among adults in Ireland

Monitoring for CKD requires regular blood and urine checks

Early detection and treatment leads to better outcomes, including prevention of the need for dialysis

Maintaining Kidney Health

Proper management of blood pressure and blood sugar levels can help keep kidneys healthy, in addition to maintaining a healthy weight

WORLD KIDNEY DAY 9th March 2023 Preparing for the unexpected, supporting the vulnerable

consequences. The data will assist new screening, referral and management pathways for CKD and increase independent living and quality of life for Irish adults.” Professor George Mellotte, National Clinical Director for Renal Services commented, “The National Renal office (NRO) proposes to use the clinical epidemiology data from this report to help inform the design of the model of care and service development for early chronic kidney disease in the

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

community and to advocate for CKD to be included as part of the National Chronic Disease Management Program.” Carol Moore, CEO of the Irish Kidney Association added, “The Irish Kidney Association congratulates the National Renal Office and TILDA for their impactful study on chronic kidney disease (CKD) in Ireland's older population. The high prevalence of CKD in those who are 50 years and older and extremely low awareness among those affected

highlights the need for more education around CKD and that it should not be viewed in isolation but rather as an integral part of other health conditions such as diabetes, high blood pressure, and cardiovascular disease. A holistic and collaborative approach will ensure better health outcomes and reduced healthcare costs. The results of the survey reinforce the Irish Kidney Association calls for CKD to be integrated into the HSE National Chronic Disease Management Programme as a crucial step forward.”

News 47

Health Action Plan ‘Won’t Hit Target’ With just weeks until the end of the year, the Irish Hospital Consultants Association (IHCA) warned last month that the Government’s ¤443 million Action Plan for 2023 will not achieve its target to reduce waiting lists for appointments and hospital treatment by 10% (-69,000), compared with the number waiting at the start of 2023. The release of the latest National Treatment Purchase Fund (NTPF) figures confirm that the three main waiting lists are at a virtual standstill, reducing by a modest 2,600 this year – a shortfall of almost 66,400. This reduction is offset by increases in other socalled ‘hidden lists’, such as the 3,490 additional people placed on the Outpatient Suspensions list in the last month alone. In total over 878,500 people were on some form of hospital waiting list at the end of November. Consultants are calling on the Government to expedite plans promised earlier this year by the Minister for Health, Stephen Donnelly TD, to urgently put in place 1,500 additional rapid build acute hospital beds and four elective hospitals in parallel with its planned surgical hubs to realistically address lengthening waiting lists. These additional 1,500 hospital beds were not funded in Budget 2024, despite calls for expressions of interest having been issued internationally by HSE officials over eight months ago for the modular builds.

Case Type

Waiting List at start of Jan 2023

Waiting List at end Nov 2023

Target Closing Waiting List at 31 Dec 2023

Difference from Target

Outpatients

584,626

580,055

520,516

59,539

Inpatient/Day Cases

81,568

84,287

79,678

4,609

GI Scopes

24,029

23,279

21,047

2,232

TOTALS

690,223

687,621

621,241

66,380

Analysis from the IHCA shows that the NTPF exceeded its target activity levels for 2023 by the end of September, commissioning at that point 44,551 inpatient or day case procedures, 21,931 gastrointestinal (GI) scopes and 164,460 outpatient appointments. It had targeted to arrange 40,000 inpatient/day case procedures, 18,500 GI scopes and 110,000 outpatient appointments in public and private hospitals this year. Despite treating significantly more patients than planned, waiting lists have remained at a virtual standstill, due to a higher-than-expected level of patient demand. The inability to accurately forecast this additional demand has contributed to the recently announced ¤1 billion supplementary budget for Health in 2023.

The 2023 Action Plan also wanted to cut the number of people on waiting lists by 146,100 without any treatment, through an NTPF ‘validation’ programme. This target, which was more than double the previous 60,000 validation target for 2022, is unlikely to be met and will impact the year end waiting list figure. Commenting on today’s waiting lists and the need for the additional hospital capacity, IHCA President Prof Rob Landers, said, “In April, the Minister for Health’s announcement of a rapid build programme to open 1,500 additional hospital beds across 15 acute public hospital sites in 2023 and 2024 was welcomed. The Government needs to implement that plan immediately and commit the promised ¤1 billion capital budget to open these beds as indicated.

“A significant ¤407 million has been allocated for next year’s Waiting List Action Plan, which is currently being finalised. However, there is nothing to suggest we won’t be in the same position come December 2024, looking back at another year of waisted opportunities to put in place realistic much increased bed and theatre capacity to address these unacceptable waiting lists and increasing number of admitted patients being treated on trolleys in EDs. “Consultants, and the patients they treat, need and deserve sustainable solutions to help alleviate the distress caused by being treated on trolleys and lengthy waiting lists. Concrete measures, as already announced, are needed to prevent poorer outcomes as a consequence of waiting too long for care.”

Radical New Approaches Needed A radical new approach to preventing chronic disease would save thousands of lives each year and protect our stretched health service, a new report insisted recently. Mandatory limits on the salt content of processed foods and a political culture which tackles vested interests in public health are recommended in a bid to confront cardiovascular disease (CVD) - Ireland’s second biggest killer. An Irish Heart Foundation position paper, compiled by UCC Professor Ivan Perry, recommends radical action – similar to Ireland’s 2004 ban on smoking in the workplace – to deal with CVD and other killer diseases.

“Little meaningful action has been taken in Ireland to truly address the key drivers of a leading cause of death and disability,” he warned the launch of the Primary Prevention of Cardiovascular Disease paper in Dublin’s Davenport Hotel.

Professor Ivan Perry

“Without the implementation of bold policy initiatives, we can expect continued and increased deaths and ill health driven by risk factors.”

A new national cardiovascular policy is also needed after the last one expired four years ago. The five core risk factors for CVD and many chronic diseases, he said, are smoking, physical inactivity, poor diet, obesity and excessive alcohol consumption.

The paper proposes mandatory limits on the salt content of bread and processed foods, a complete online ban on marketing of high fat, sugar and salt food and drinks and an increase in the legal age of tobacco sales from 18 to 21.

Prof Perry’s findings are being supported by the Irish Health Promotion Alliance (IHPA) - a new coalition launched at the same event to highlight the devastating impact CVD, cancer and diabetes is having on the nation.

Members include the Irish Heart Foundation, Irish College of General Practitioners, Irish Medical Organisation, Royal College of Surgeons in Ireland, Irish Cancer Society, Alcohol Action Ireland.

HOSPITALPROFESSIONALNEWS.IE | HPN • JANUARY 2024

48 Diabetes News

Advocacy as a Main Priority for Diabetes Ireland Advocacy was once again a main priority of Diabetes Ireland during 2023. In publishing their Annual Report, they summarised the work and activities in the areas of diabetes advocacy, education, support and awareness. “Our aim is to see improved public services, better and quicker access to good quality care, diabetes technology and medications, and better recognition of diabetes and the diabetes community by the Government and its public officials. Work is continuously ongoing to achieve improvements that will benefit the diabetes community,” said a spokesperson. Diabetes Ireland also called for the setting up of a diabetes task force to develop a 10-year National Diabetes Strategy that provides vision, leadership, and direction so that the HSE can recruit the staff required and improve the quality of life for people living with diabetes and reduce the long-term costs to the health service of diabetes complications. We are hopeful that we will see this come to fruition in the near future. Earlier this year, Diabetes Ireland attended a reception at the Irish Embassy in London to celebrate the 150th anniversary of The Hospital Saturday Fund, Diabetes Ireland was a beneficiary of a grant which went towards their “Teen Activity Day 2023”.

The reception was hosted by Ambassador Martin Fraser. The Hospital Saturday Fund donated a total of £160,000/¤176,000 to thirty-one medical charities and organisations from Ireland and the UK during the event. The occasion was made even more special with the presence of Graham Norton, a celebrity supporter of Bantry Hospice, who presented the donations. Lesley Garrett, the Patron of The Hospital Saturday Fund, also participated in making the presentations to the recipient charities. The association’s Teen activity day returned for 2023. 65 teenagers over 3 venues across the country, supported by diabetes nurses, volunteers and Diabetes Ireland staff ensured a fantastic day was had by all. With all the teens doing a series of land and water-based activities, archery, football, wall climbing, Boda Borg, kayaking, surfboarding and good old pier jumping, everyone made lots of new friends making it a great day for all.

days,” said Kieran O’Leary, CEO, of Diabetes Ireland. It was with great sadness during 2023 that Diabetes Ireland marked the passing of President Professor Gerard Tomkin. Professor Tomkin saw a need for Diabetes Ireland to become a strong voice in advocating for people with diabetes and growing the charity so it would be more supportive to people living with diabetes. He was also very much aware of the increasing prevalence of Type 2 diabetes and the huge impact it would have on the health service and the importance of promoting a healthy lifestyle for all the family, not just people living with diabetes. In recent years, Professor Tomkin continued to work closely with Diabetes Ireland as an active President and Board Member offering his support to staff and volunteers. He was a regular visitor to Santry always engaging with staff individually, making sure they were happy and content and was very giving of his time to everyone. In particular, he thoroughly enjoyed

A huge thank you to the Hospital Saturday Fund and to the parents who fundraise for Diabetes Ireland which allowed them to hold this event. The aim of the day is to bring together young teenagers living with diabetes to have a fun day and to meet other teens with diabetes. “To date, 40 teenagers have registered, and we hope to see more register in the coming

attending the 50-year “Living With Diabetes” medal ceremonies meeting many of his older patients and sharing their stories and memories of life with diabetes. Towards the end of this year, a new collaborative campaign between Diabetes Ireland and the Irish Childhood Diabetes National Register, supported by Norah Casey, Professor Edna Roche, Consultant Paediatrician and Endocrinologist alongside diabetes advocates Eva Lee and her son Danny and Jay Hickey aims to raise awareness among the general public about the symptoms of Type 1 diabetes, equipping individuals to recognize these signs early, seek help and avoid the development of Diabetic Ketoacidosis (DKA). To raise awareness of the symptoms of Type 1 diabetes the team have developed an acronym, TEST, which stands for Thirst (increased), Energy (reduced), Sudden (weight change), and Toilet (trips increased).

Teen Activity Day

Remembering Professor Gerald Tomkin

Fundraising: Paul Jackson, Chief Executive, The Hospital Saturday Fund with Diabetes Ireland CEO Kieran O’Leary, Ambassador Martin Fraser, Graham Norton and guests

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

Norah Casey, Professor Edna Roche, Consultant Paediatrician and Endocrinologist, Eva Lee and her son Danny and Jay Hickey

10 years of experience in Ireland2

XTANDI is indicated for the treatment of adult men with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgen - deprivation therapy, in whom chemotherapy is not yet clinically indicated.2 XTANDI is also indicated for the treatment of adult men with metastatic castration-resistant prostate cancer whose disease has progressed on or after docetaxel.2 Ireland and Northern Ireland Abbreviated Prescribing Information: XTANDITM (enzalutamide) 40 mg film-coated tablets. For full prescribing information, refer to the Summary of Product Characteristics (SPC). Presentation: 40 mg film-coated tablets each containing 40 mg of enzalutamide. Indications: The treatment of adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy. The treatment of adult men with high-risk non-metastatic castration-resistant prostate cancer (CRPC). The treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy. Posology and administration: Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets) as a single oral daily dose. The tablets should be swallowed whole with water, and can be taken with or without food. Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients not surgically castrated. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SPC. Women who are or may become pregnant. Special warnings and precautions for use: Risk of seizure: Use of enzalutamide has been associated with seizure. The decision to continue treatment in patients who develop seizures should be taken case by case. Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving XTANDI. PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of XTANDI in patients who develop PRES is recommended. Second Primary Malignancies: Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide. Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment. Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations. Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If XTANDI is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Renal impairment: Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment: An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction may be increased. Recent cardiovascular disease: The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if XTANDI is prescribed in these patients. Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating XTANDI. Use with chemotherapy: The safety and efficacy of concomitant use of XTANDI with cytotoxic chemotherapy has not been established. Coadministration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenous docetaxel; however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded. Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema have been observed with enzalutamide. Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. Excipients: This medicine contains less than 1 mmol sodium (less than 23 mg) per film-coated tablet, that is to say essentially ‘sodium-free’. Interactions: Potential for other medicinal products to affect enzalutamide exposures: CYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite. Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. No dose adjustment is necessary when XTANDI is co-administered with inducers of CYP2C8. CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when XTANDI is co-administered with inhibitors or inducers of CYP3A4. Potential for enzalutamide to affect exposures to other medicinal products: Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5’-diphospho-glucuronosyltransferase (UGTs - glucuronide conjugating enzymes). Some transporters may also be induced, e.g. multidrug resistance-associated protein 2 (MRP2) and the organic anion transporting polypeptide 1B1 (OATP1B1). In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19 or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate. In consideration of the long half-life of enzalutamide (5.8 days), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment. In vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. A mild inhibitory effect of enzalutamide, at steady-state, on P-gp was observed in a study in patients with prostate cancer that received a single oral dose of the probe P-gp substrate digoxin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC and Cmax of digoxin increased by 33% and 17%, respectively. Medicinal products with a narrow therapeutic range that are substrates for

P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with XTANDI and may require dose adjustment to maintain optimal plasma concentrations. At steady state, enzalutamide did not cause a clinically meaningful change in exposure to the probe breast cancer resistance protein (BCRP) substrate rosuvastatin in patients with prostate cancer that received a single oral dose of rosuvastatin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC of rosuvastatin decreased by 14% while Cmax increased by 6%. No dose adjustment is necessary when a BCRP substrate is co administered with XTANDI. Based on in vitro data, inhibition of MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of XTANDI with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated. Fertility, pregnancy and lactation: There are no human data on the use of XTANDI in pregnancy and this medicinal product is not for use in women of childbearing potential. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential a condom and another form of birth control must be used during and for 3 months after treatment. Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. It is not known if enzalutamide is present in human milk. Enzalutamide and/ or its metabolites are secreted in rat milk. Animal studies showed that enzalutamide affected the reproductive system in male rats and dogs. Effects on ability to drive and use machines: XTANDI may have a moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported. Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines. Undesirable effects: Summary of the safety profile: The most common adverse reactions are asthenia/ fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include ischemic heart disease and seizure. Seizure occurred in 0.5% of enzalutamide-treated patients, 0.2% of placebo-treated patients, and 0.3% in bicalutamide-treated patients. Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients. Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Adverse reactions are presented according to Medical Dictionary for Regulatory Activities (MedDRA) system organ classification and within each frequency grouping they are presented in order of decreasing seriousness. Adverse reactions identified in controlled clinical trials and post-marketing: Blood and lymphatic system disorders: Uncommon: leucopenia, neutropenia; Not known*: thrombocytopenia. Immune system disorders: Not known*: face oedema, tongue oedema, lip oedema, pharyngeal oedema Psychiatric disorders: Common: anxiety; Uncommon: visual hallucination. Nervous system disorders: Common: headache, memory impairment, amnesia, disturbance in attention, dysgeusia, restless legs syndrome; Uncommon: cognitive disorder, seizure¥; Not known*: posterior reversible encephalopathy syndrome. Cardiac disorders: Common: ischemic heart disease†; Not known*: QT-prolongation. Vascular disorders: Very common: hot flush, hypertension. Gastrointestinal disorders: Not known*: nausea, vomiting, diarrhoea. Skin and subcutaneous tissue disorders: Common: dry skin, pruritus; Not known*: erythema multiforme, rash. Musculoskeletal and connective tissue disorders: Very common: fractures‡; Not known*: myalgia, muscle spasms, muscular weakness, back pain. Reproductive system and breast disorder: Common: gynaecomastia. General disorders and administration site conditions: Very common: asthenia, fatigue. Injury, poisoning and procedural complications: Very common: fall. * Spontaneous reports from post-marketing experience. ¥ As evaluated by narrow Standardised MedDRA Queries (SMQs) of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures and status epilepticus. This includes rare cases of seizure with complications leading to death. † As evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia and arteriosclerosis coronary artery. ‡ Includes all preferred terms with the word ‘fracture’ in bones. Description of selected adverse reactions: Seizure: In controlled clinical studies, 24 patients (0.5%) experienced a seizure out of 4403 patients treated with a daily dose of 160 mg enzalutamide, whereas four patients (0.2%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a doseescalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. In the 9785 CL 0403 (UPWARD) single-arm trial to assess incidence of seizure in patients with predisposing factors for seizure (whereof 1.6% had a history of seizures), 8 of 366 (2.2%) patients treated with enzalutamide experienced a seizure. The median duration of treatment was 9.3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA-gated chloride channel. Ischemic Heart Disease: In randomized placebo-controlled clinical studies, ischemic heart disease occurred in 3.9% of patients treated with enzalutamide plus ADT compared to 1.5% patients treated with placebo plus ADT. Fifteen (0.4%) patients treated with enzalutamide and 2 (0.1%) patients treated with placebo had an ischemic heart disease event that led to death. Prescribers should consult the full SPC in relation to other adverse reactions. Overdose: There is no antidote for enzalutamide. In the event of an overdose, treatment with enzalutamide should be stopped and general supportive measures initiated taking into consideration the half-life of 5.8 days. Patients may be at increased risk of seizures following an overdose. Cost (excluding VAT): XTANDI 40 mg film-coated tablets x 112: Ireland: POA. Northern Ireland: £2,734.67. Legal classification: Ireland: POM/S1A. Northern Ireland: POM. Marketing Authorisation number: XTANDI 40 mg film-coated tablets: EU/1/13/846/002 Marketing Authorisation Holder: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands. Date of preparation of Prescribing Information: October 2022 Job number: MAT-UKE-XTD-2022-00004 Further information is available on request from: Ireland: Astellas Pharma Co. Ltd., Tel.: +353 1 467 1555. Northern Ireland: Astellas Pharma Ltd, Medical Information 0800 783 5018. For full prescribing information, refer to the SPCs, which may be found at www.medicines.ie (Ireland) and https://www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland). Adverse events should be reported. For Ireland, Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance, Website: www.hpra.ie or Astellas Pharma Co. Ltd. Tel: +353 1 467 1555, E-mail: irishdrugsafety@astellas.com. Adverse events should be reported. For Northern Ireland, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Astellas Pharma Ltd on 0800 783 5018.

*Calculated from global sales data and real-world data. References: 1. Astellas Data on File – MAT-ABC-XTD-2023-00061. 2. XTANDI (enzalutamide) Summary of Product Characteristics.

MAT-IE-XTD-2023-00087 Date of preparation: September 2023

50 Ovarian Cancer

Multidisciplinary Approaches to Ovarian Cancer Mater Hospital research shows multidisciplinary surgical approach to advanced ovarian cancer significantly reduces death rate and progression of disease Professor Donal Brennan, Consultant Gynaecological Oncologist at the Mater Hospital and Professor of Gynaecological Oncology at UCD School of Medicine

A multidisciplinary surgical approach implemented by gynaecological oncology experts at the Mater Hospital has improved outcomes for women with advanced ovarian cancer to the extent that patients are approximately 70% less likely to die three-years post surgery. The new study published in the Annals of Surgical Oncology, which also noted a decrease in rates of disease progression, focused on two cohorts of patients diagnosed with advanced ovarian cancer and treated at the Mater Hospital from 2006-2015 and 2017-2021 respectively. In 2017, the Mater Hospital’s Department of Gynaecological Oncology adopted a multidisciplinary surgical approach to patients with advanced ovarian cancer which has allowed for greater rates of cytoreduction, or complete removal of all sites of cancer within the abdominal cavity. As a result, this study has noted a decrease in the mortality rate from 64.5% of patients three-years post surgery to 24%.

“Extensive surgery is often required and we believe that collaboration between different surgical specialities allows us to safely perform aggressive operations to remove all visible tumours from the abdomen which is the single greatest predictor of improved survival” Senior author of the study, Professor Donal Brennan, Consultant Gynaecological Oncologist at the Mater Hospital and Professor of Gynaecological Oncology at UCD School of Medicine, said, “Ovarian cancer is a complicated disease that requires input from multiple specialties including medical oncology, pathology, radiology and surgery. Extensive surgery is often required and we believe that collaboration between different surgical specialities allows us to safely perform aggressive operations to remove all visible tumours from the abdomen which is the single greatest predictor of improved survival. The study

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

supports the growing body of international evidence that patients with ovarian cancer have better outcomes when managed in centralised specialised oncology centres, such as the Mater.” In order to combat late-stage disease, the collaborative multidisciplinary environment allows for gynaecological oncologists as well as colorectal, hepatobiliary and upper gastrointestinal surgeons to carefully plan surgical resections and subsequent treatment. These types of complex surgeries involve multiple specialists and can take up to ten hours to perform. This new research also shows that disease progression three years after surgery and chemotherapy has reduced from 75% in the first cohort of patients, to under 50% in the second - a decrease of more than 35%. Jürgen Mulsow, Consultant General and Colorectal Surgeon at the Mater, said: “As part of our multidisciplinary approach to advanced cancer, we at the Mater Hospital collaborate with colleagues to select the most suitable patients for surgery. This collaboration ensures that patients receive integrated medical care from the moment of consideration of surgery to full recovery and has helped us to improve both peri-operative and long-term outcomes.” The study marks a positive step in the treatment of ovarian cancer, which is the seventh most prevalent female cancer globally and frequently presents at an advanced stage due to lack of symptom awareness. Historically, survival rates for ovarian cancer in

Ireland have significantly lagged behind our European neighbours. In May 2017, Jeannine Davis from Coolock in Dublin, received a diagnosis of advanced ovarian cancer at the age of 39. Speaking about her care at the Mater, Jeannine said: “The only symptom I had of ovarian cancer was a swollen stomach and I was devastated to learn of my diagnosis. However, the silver lining was meeting with the gynaecological oncology team at the Mater who saved my life. I felt that I was in good hands as they meticulously planned my surgery and follow-up treatment. I encourage women to listen to their bodies and make themselves aware of the signs of gynaecological cancers.” The UCD Gynaecological Oncology Group at the Mater Hospital has been certified as a centre of excellence for ovarian cancer in Europe. To date, as the National Centre for Peritoneal Malignancy and home to the largest ovarian cancer unit in the UK and Ireland, the Mater Hospital has performed more than 250 major cytoreductive surgeries on patients with advanced ovarian cancer. Alan Sharp, CEO of the Mater Hospital, added, “I am proud of the great strides that my colleagues at the Mater Hospital have made in the pursuit of better patient outcomes for patients with ovarian cancer. As a leading teaching and research hospital, we are maintaining our strong track record of producing high quality treatments that deliver real and meaningful results to patients and their families.”

Childhood Obesity 51

Managing Childhood Obesity: The Important Role for Pharmacists Obesity is a challenge to most health systems across the world, and international and national health strategies address the prevention, treatment and ongoing care needs for those with obesity. Obesity is defined as “abnormal or excessive fat accumulation that presents a risk to health”.1 Diagnosing obesity in children requires: 1) an assessment of the volume and location of adipose tissue. At a practical level we assess fat tissue using the proxy measurement of body mass index (BMI). We then plot the BMI on age- and sex-adjusted BMI charts. The use of growth charts in childhood is essential. 2) assessment of body systems to determine whether the health of the child is affected by the level of fat tissue or having a body weight above a healthy level. Clinical assessment usually includes assessment of blood pressure and cardiovascular health, overall child development, cardiorespiratory health, musculoskeletal health, gastrointestinal health and mental health.

In Ireland 19% of primary school children and 26% of adolescents have body mass indices in the overweight or obese categories and children who attend schools with lower socioeconomic position have nearly double the likelihood of having obesity.2,3

Written by Dr Grace O’Malley, Clinical Lead, Child and Adolescent Obesity Service, Children’s Health Ireland/Principle Investigator, RCSI Obesity Research and Care Group

Childhood obesity is concerning during childhood as it is linked to: • Health difficulties as the child grows and develops (e.g. joint pain, breathing difficulties, skin problems, urinary incontinence) • A higher risk of developing other chronic diseases in adulthood (e.g. certain cancers, type-2 diabetes, coronary heart disease) • A higher risk of having obesity as an adult See Figure 1 from Wyse et al Due to the higher risk of health complications associated with childhood obesity, early diagnosis and treatment for obesity are important. A major challenge for health professionals is that few are trained in the area of obesity management. As such it is essential that all

health professionals complete basic training in this area. All pharmacists are welcome to complete the Online Childhood Obesity Training Course. The course includes a core module (1 hour) and four advanced modules (1 hour each) and is free of charge through the website www.childhoodobesity.ie. Up to five FREE CPD points can be earned. Sometimes parents are unsure as to whether their child has obesity or not. It is important therefore, to appreciate the difference between a child whose body weight is

above a healthy level for their age but has no health complications (is healthy) versus one who has a body weight above a healthy level PLUS health complications. Parents are often unsure where to go for information and the community pharmacist can play a key role in sharing evidencebased information with families and sign-posting families to suitable resources.

Figure 1 Health Complications Associated with Obesity in Childhood

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8 Healthy Habits

52 Childhood Obesity Pharmacist Role 1: using sensitive verbal communication In 2014, a survey of Irish GPs indicated the majority found it difficult to broach the issue of childhood overweight during consultations. However when GPs started measuring growth in 5-12 year olds attending for unrelated care, parents and children did not find it traumatising, and over 98% of parents indicated this was both useful and acceptable.4 If a family attends the pharmacy and expresses concerns around childhood weight, overweight or obesity the pharmacist can play a key role in addressing the topic appropriately through use of sensitive, respectful and appropriate communication.

Get enough sleep Recommended over 24 hours: 10-13 hours for 3-5 years; Recommended per night: 9-11 hours for 5-13 years; 8-10 hours for 14-17 years.

Pharmacist Role 2: providing growth measurement Depending on the type of pharmacy offering childhood growth measurement might be appropriate. In order to measure growth, pharmacies need to have a weighing scales and an appropriate height measure. In addition they need access to childhood growth charts which are available online (see example below). For a child over 2 years of age, the BMI-for-age centile is a more sensitive indicator of weight issues than the weight centile. A child who is plotted above the 91st centile on the BMI centile falls in the overweight category. A child who is plotted above the 98th centile on the BMI centile is in the very overweight/obesity category. Velocity of physiological weightgain varies between gender, therefore BMI-for-age charts are different for boys and girls. Of note, the BMI cut-offs for children are not the same as adults, and as such, the

(180 mins per day broken

Start each day with a healthy breakfast

into shorter blocks for <5 years)

Be healthy together

1 hour

Parent: “I’m worried about my child’s weight – I think she is too heavy”

Note: Depending on the situation, it may be more appropriate to avoid speaking about growth in front of the child. In such cases you may decide to advice mum to make an appointment with the child’s GP.

Aim to eat at least 5 portions of vegetables and 2 portions of fruit every day. For 2 year olds, eat 2- 3 portions of fruit and vegetables daily. For 3-4 year olds eat 4-5 portions of vegetables and fruit daily.

1 Be active for at least 1 hour a day, every day

Example 1: Addressing parental concern

Pharmacist: “Children are growing and developing all the time so we would need to check what her growth is like compared to others her age. It’s good that you are thinking about her growth as sometimes children will have difficulties with their health if they gain weight faster than height. If you like we could measure her growth and check it on the growth chart?”

Drink water instead of soft drink, juice or cordial

6 5 2 hours Limit screen time and take movement breaks after 30 mins of sitting. No more than 1 hour a day for 2–5 year olds, and up to 2 hours a day for children 6 years and older. Choose healthier snacks and fewer treat foods

Use child sized portions

Fig 2. Healthy habits for healthy child growth and development

BMI-for-age centiles should be used (e.g. a 13 year old boy with a BMI of 24.3kg/m2or a 5 year old girl with a BMI of 20kg/ m2 both plot above the 98th centile on respective sex-adjusted BMI-for-age charts). Both of these examples fall in the very overweight/obesity category. Example 2: Offering/suggesting growth measurement Parent: “Yes could you check how much she weighs please?” Pharmacist: “It’s important that we check weight and height so that we can track her growth over time. We need to check how tall she is and how much she weighs. Then we will calculate her body mass index and check it on the growth chart. After that, you may need to visit your GP for more advice” Note: For growth monitoring training see free courses at www. childhoodobesity.ie and HSELand Do not offer child/adolescent

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growth measurement if you have not been trained how to do this. You can use online age- and sexadjusted growth charts to plot weight, height and BMI. You could also signpost the parent to an online growth calculator. Pharmacist Role 3: explaining treatment options With increased attention on antiobesity medicines used for adults, some parents may be requesting access to these treatments for their children. It’s crucial that parents are informed about the appropriate treatment options for children and teenagers. The current evidence-base suggests that children and teenagers be offered structured conservative treatment as the first step and all health professionals should be aware of the key targets for such treatment (see Fig 2): • Getting enough sleep each night for the child’s age

• Drinking enough water and milk, avoiding sugar-sweetened drinks • Eating child-sized portions of a wide variety of foods at regular times each day (usually 3 meals per day + 2 healthy snacks) • Playing actively for 60 mins or more each day • Limiting screen time (especially when eating meals and before/at bed-time) • Limiting the amount of sitting each day Example 3: Clarifying appropriate treatment Parent: “I’d like to get her some anti-obesity drugs. I’ve heard they work really well” Pharmacist: “The obesity drugs available at the moment are approved for adults. In rare cases if children have signs of type-2 diabetes their hospital doctor

53 may prescribe an anti-obesity medication, so you should chat to your GP about that. For now, treatment should start with making sure she gets the right amount of sleep, play and nutrition for her age. I can show you where to find some helpful tips if you like?” Note: You could print out the 8-healthy tips infographic or signpost parents to this information available from the childhood obesity training website of to the Safefood Guide for Family Health https:// www.safefood.net/family-health Pharmacist Role 4: Signposting and onward referral If parents report that the child has any difficulties with their development (e.g. speech,

walking, vision, hearing or learning) the pharmacist should confirm whether the child has a GP. If so, a visit to the GP is recommended. If the child does not have a GP, the pharmacist should recommend that the parent register the child with a local GP and that a visit should be booked in order to check the child. Parents should be made aware that most GP practices offer free services to children under 8-years of age. Parent: “I know my son is overweight but I don’t know what to do. I’m worried about him” Pharmacist: “It’s good that you are thinking about your sons health and development. Some children have a body weight above

a healthy level for their age and because of this they can have some difficulties with their health. I can suggest some information for you to read and tips to follow but it is really important that you bring him to the GP for a health check. Is he registered with a GP or a public health nurse?” In summary, pharmacists can play an important role in helping families make decisions about trying to access appropriate health information, clinical assessment and treatment to support healthy child growth and development. In addition, pharmacists are key members of the multi-disciplinary health team and should be supported to access free training in this important area of practice.

Resources • Up to date advice, tools, online training and research on childhood obesity prevention and treatment: https://childhoodobesity.ie/ resources/ • Booklet for children and families that provides lifestyle advice needed in a friendly, non-judgemental and engaging way: https://w82go.ie/wpcontent/uploads/2021/01/W82GObooklet-20112020.pdf • Safefood Ireland website have excellent videos, helpful for parents struggling with literacy, as well as friendly accessible material on good eating habits and food preparation https://www.safefood.net/familyhealth/active-at-home • HSE Model of Care for Adult and Paediatric Obesity (2021)5 https:// www.hse.ie/eng/about/who/cspd/ ncps/obesity/model-of-care/

References available on request

News Groundbreaking National Skin Cancer Service Being Blocked A hi-tech skin cancer service, which could provide rapid treatment for patients, has still not been fully taken up by more than two thirds of the 13 national dermatology departments, despite its uptake in Dublin hospitals. The service, which is provided by AllView Healthcare, offers skin cancer and medical skin treatment services using cutting edge technology. Mr Eoin O’Reilly, CEO AllView Healthcare commented, following direct recent conversations with Minister for Health, HSE Acute Services and local hospital management teams all of whom have been trying to get the service started for over a year, that the project is being directly blocked by local key personal within some of the dermatology departments. Dublin hospitals such as St. James’s Hospital, Beaumont Hospital and Connolly Hospital Blanchardstown, along with Our Lady of Lourdes Hospital Drogheda, have all used AllView’s Teledermatology service to drastically reduce waiting lists, by treating over 15,000 HSE patients in the last two years. Allview Healthcare have today confirmed renewal of its HSE contract to deliver capacity for a further 20,000 patients who are currently on hospital public waiting lists, to access its dermatology service in Ireland for 2024. This is a continuation of previously awarded contracts which, in 2022, resulted in AllView significantly reducing dermatology waiting lists in 5 hospitals.

Dr Rupert Barry, Consultant Dermatologist & Co-founder AllView Healthcare, and Eoin O’Reilly, CEO & Co-founder, AllView Healthcare, pictured with Nora Chiorascu, Head of Operations and Jennifer Luke, Project Manager

Mr Tony O’Brien, former Director General of the HSE, is a board member of AllView Healthcare and heads up its Medical Governance Committee thereby ensuring patient-focused best practice compliance is maintained at all times. The increase in patients waiting for their first appointment increased from September 2023 to October 2023 by 1,293 patients. The overall public patient waiting list for first time dermatology appointments currently stands at 54,488 and has increased month on month for the last ten months by a total of 8,484 patients. Over 10,000 public patients are waiting more than 12 months for their first appointment. (Source: National Treatment Purchase Fund, September 2023 / www.ntpf.ie) Allview Healthcare had the ability to see and treat 20,000 patients across Ireland in 2023 for the HSE, yet only less than 4,000 patients were sent to the service nationwide by hospitals. With such grave concerns being voiced by GPs across the country such as the recent outburst from local GPs in Letterkenny and Sligo, CEO Mr. O’Reilly, said that despite regular positive

interactions with both the HSE and local hospital management wanting to deploy its services, the blockage to the green light being given for their service to go live in certain hospitals, is being held up directly within the dermatology departments itself within each hospital for reasons unknown.

in sufficient numbers to make any noticeable difference to the dermatology waiting lists despite being awarded public contracts, and having huge unused capacity on hold for the HSE.”

AllView were recently awarded a major contract for the provision of dermatology services by the VHI Healthcare, under which it now offers members an appointment within 10 days, and a consultation with treatment, including surgery if required, within weeks.

Mr O’Reilly, also stated, “It is shocking that a few key staff within any department hold the power to block patients access to such service and stopping the hospital management from deploying such a modern and proven service like ours, when their current waiting time to see a patient is several years duration.

Our service is enabling patients to be quickly seen and treated. Mr O’Reilly said, “We wish to also make a significant contribution to the reduction of public dermatology waiting lists; however, we first need to be sent the patients by the hospitals to treat those patients. Patients are not referred to us

“We have local nationwide clinics where we can see and treat patients. We have had over 100 melanoma patients last year, with Breslow thickness of our cancer patients the lowest in the country at 0.68mm, proving early access to care have lifesaving outcomes for patients.”

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54 News

Mater Private Cork Celebrate an Ireland ‘First’ at the hospital has doubled and it now has over 100 beds, among those 65 state-of-the-art inpatient single en suite rooms, setting a new standard for private healthcare in Munster.

Sandra Daly, CEO of Mater Private Cork, celebrates 10 years in operation with members of Mater Private Cork Management Just last month, Mater Private Cork celebrated the official opening of its second Cardiac Catheterisation Laboratory and in doing so, becomes the first private hospital in the region to boast two Cath Labs. The culmination of a ¤4.8 million investment programme, the move further cements Mater Private Network’s position as a national leader for cardiac care, and significantly expands its capacity for treating both complex and routine cardiac cases in Munster. Heart disease is the number one cause of death in Ireland and with an ageing population and increasing prevalence of chronic health conditions the demand for heart disease treatment has never been greater. Mater Private Network is a national tertiary referral centre for cardiac

intervention, and as one of the busiest high volume cardiac and vascular centres in the country, delivers intervention, testing and surgical services across a network of hospitals, ambulatory clinics and outreach centres. To date, almost 25,000 invasive cardiac procedures have been performed at the hospital in Cork and this investment will double patient access to interventional procedures on site. Over the last decade, Mater Private Network has shown an unwavering commitment to delivering exceptional healthcare in Cork and through consistent and strategic investment to the value of ¤25 million, has delivered an exponential growth of services paving the way for unprecedented patient access to complex treatments. Treatment capacity

Key milestones since the hospital’s establishment ten years ago include the opening of the first Cath Lab in 2014, the opening of the Urgent Cardiac Care service in 2015 and Emergency Department in 2016, the specialised Spine & Orthopaedic Centre and Ophthalmology Centre in 2017 and most recently, the establishment of the Centre for Women's Health, the first of its kind in a hospital setting here in Ireland, which opened its doors to the women of Munster in May 2022. Commenting on Mater Private Network’s impact in the region, CEO of the Mater Private Cork, Sandra Daly commented, “Through consistent and strategic investment, we have expanded our services in Cork and now treat over 74,000 patients annually from the wider Munster region. Just last month we were awarded the Joint Commission International Gold Standard Accreditation (JCI) for the fourth time, a testament to the exceptional standard of care and operational excellence on site. “Building a team of over 400 employees, 74 specialist consultants among them, has been essential to that success. I’m delighted to be presenting 46 commemorative medals to members of staff this Friday to

celebrate those have completed 10 years of service with us since our establishment in 2013. Our culture and values put the patient at the heart of everything we do, and we have great ambitions for the next ten years.” Speaking about Mater Private’s cardiology services, Dr. Ronan Margey, Clinical Lead and Consultant Cardiologist at Mater Private Cork, added, “Mater Private Cork continues to deliver the highest quality cardiac care to thousands of patients each year and is a recognised regional centre for complex, high-risk interventional procedures for coronary artery disease. This investment of ¤4.8 million represents a critical first step in the expansion of our cardiology services. The second Cath Lab will facilitate the expansion of our Urgent Cardiac Care service and deliver a twofold increase in the volume of cardiac patients we can treat here. “In 2024 we plan to expand our advanced cardiac diagnostic imaging, establish an Intensive Care Unit and offer cardiac surgery on site. This step will uniquely position Mater Private Cork to provide 360-degree comprehensive cardiac care to patients across the wider Munster region. We will of course also continue to offer our patients access to multiple clinical research trials of new treatments and new technologies as part of our research collaboration with the Cardiovascular Research Institute (CVRI).”

Oesophageal cancer Treatment Research New research from RCSI has revealed that oesophageal cancer patients with an apparent complete response after chemotherapy and radiotherapy, and who choose not to have surgery, have a similar outcome to patients choosing surgery. The study, published in the British Journal of Surgery, examined the outcome choice for patients with cancer of the oesophagus and shows that forgoing surgery may be the better option for older patients. It was inspired by a patient of Professor Thomas Walsh, Emeritus Professor of Surgery at RCSI, who prompted him to involve patients more directly in decision making about surgery after other cancer treatments.

Professor Walsh explained, “The inspiration came from a lovely lady, Eileen, who listened to me patiently when I told her that I would arrange for chemotherapy and radiotherapy, and I would then operate on her. But she said ‘No, you won’t! You will give me chemotherapy and radiotherapy, but you won’t operate. Because my sister had the same tumour, and had a very good response to the treatment, but then they operated, and she died’.

oesophageal cancer patients, but the surgery is complex and can be risky for patients, who may even die from complications. And quality of life is poorer after surgery”, says Professor Walsh.

“So, I respected her choice and followed her up very closely. She was 74 then and lived another 17 years before dying of natural causes. I’m glad I listened to her.

“When biopsy samples showed no obvious cancer in the oesophagus, and the CT scan is clear, there might still be microscopic amounts present, or cancer cells may have already spread to other sites in the body. But one third of patients will have no cancer in the oesophagus when it is removed. It's an ethical dilemma.”

“Chemotherapy combined with radiotherapy and surgery has improved survival rates of

Patients in the study were invited to choose: to have surgery to remove the oesophagus (in case there was

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

still cancer present), or to avoid surgery, keep the oesophagus and be closely monitored. The study showed that while patients in their 50s and 60s were more likely to want surgery to be certain that the disease was gone, older patients, in their early 70s and above, were less likely to choose surgery and its potential side-effects. The patients that chose surveillance had comparable survival rates to patients who chose surgery. The RCSI research team that carried out the study in Beaumont and Connolly Hospitals were Professor Thomas Walsh, Natallia Kharytaniuk, Heidi Furlon.

News 55

Flying Doctor Praises Care received at TUH Dubbed the flying doctor, Ron Grainger set not one but two world records winning gold in the 100 and 200m at the World Transplant Games in Perth earlier this year. What is even more remarkable perhaps is that Ron was competing in the 70 -79 age category, 20 years after he received a kidney transplant. To mark this milestone Ron returned to the Vartry Renal Unit in TUH to present the Renal team with a special presentation of one of his gold medals. Commenting on the presentation Professor George Mellotte, Consultant Nephrologist said, “This is an incredibly generous gesture by Ron to the Vartry Renal Unit in TUH. The gold medal is a very visible and impressive symbol of what can be achieved by someone living with a kidney transplant. It is incredibly important to maintain a healthy lifestyle after a transplant and Ron has well and truly gone the extra mile in what he

Professor George Mellotte and Ron Grainger

has a achieved, he is an inspiration to all of the medical team and I am sure our patients getting treatment in our Unit will be equally inspired by his achievements.” The World record holder and kidney transplant patient worked for many years as a Consultant Urologist at Tallaght University Hospital (TUH), during which time he was also treated by the Hospital’s Nephrology team. Ron was diagnosed with an inherited degenerative kidney disorder at the age of 32 and

was aware that by his early 50s, he would develop end-stage renal failure and require renal replacement therapy, either dialysis or transplant. Ron says, “As chronic renal failure became a reality, my fitness levels deteriorated significantly. Receiving a kidney transplant at the age of 53 changed that. Within

nine weeks post-transplant, I returned to an extremely busy job as a Consultant Urologist here at TUH.” Ron had moved to TUH from the old Meath Hospital in Dublin City. He worked in TUH for 14 years before retiring and has been answering some of our questions following his record-breaking year.

Retirement of Martin Varley The Irish Hospital Consultant Association (IHCA) would like to announce the retirement of its Secretary General, Martin Varley. Martin has dedicated 17 years of his career to the Association, over twelve years of this as our General Secretary. Throughout, he has led with dedication and determination. During Martin’s tenure, IHCA membership has doubled, with 95% of hospital consultants working in Ireland now represented by the Association. Martin played a central role in negotiating crucial agreements with government and a large range of healthcare organisations, including the most recent Consultant contract. In doing so, he always sought to highlight and advance the interests of our members and the patients we care for. Martin’s leadership has been invaluable in the very challenging austerity period, in the advocacy for increased acute hospital and mental health service capacity. This included the Association’s successful High Court action in 2018, rectifying the State’s breach of contract in 2009. This accomplishment alone was instrumental in addressing the break in trust by upholding the rights and interests of our members.

Martin Varley

IHCA President, Professor Rob Landers has paid tribute to Martin Varley for his outstanding service and unwavering dedication. “Through our #Carecantwait campaign, Martin was central in shining a light on the severe capacity deficits in public hospitals and mental health services. This campaign has played a pivotal role in advocating for increased investment in our healthcare services which are needed to ensure timely care for patients. “The process to recruit a new Secretary General now commences and we will update members further on our progress on this front in the new year. “On an interim basis, our Assistant Secretary General Alice McGarvey and Senior Executive Officer Aidan O’ Reilly will jointly act as Secretary General, ensuring continuity of our Association's operations and meeting the needs of our 3,700 members.” Speaking following the announcement of his retirement Martin Varley said, “It has been a privilege to contribute to the

growth and success of the Irish Hospital Consultants Association. I am very proud of all we have achieved together throughout my 17 years. “I am confident that under the interim and new leadership, along with the dedication of all our

members, the Association will continue to thrive. “I would like to thank all our members; it has been an honour to work alongside professionals who are so dedicated to delivering improved and better healthcare for all.”

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56 News

Facilitating Innovation in Healthcare Dr Seamus Morris, Consultant Orthopaedic Spine Surgeon & Director of Innovation at the Pillar Centre for Transformative Medicine in the Mater Hospital; Prof John R. Higgins, HIHI Principal Investigator, CEO South/South West Hospital Group and UCC Professor of Obstetrics and Gynaecology; Erin Daly Operations Manager, the Pillar Centre for Transformative Healthcare, ERIL (Eccles Research Innovation Ltd.) & DERI ( Directorate for Education, Research and Innovation); Dr Tanya Mulcahy, Director Health Innovation Hub Ireland; Prof. Brendan Kinsley, Clinical Director of the Pillar Centre for Transformative Healthcare & DERI; Dr Steven Griffin, Manager Health Innovation Hub Ireland Galway.

with commercial and corporate entities around device design and medtech development has also progressed such that a number of companies are collaborating with Mater Innovators in areas such as Oncology, Breast Cancer and Spinal surgery. Health Innovation Hub Ireland (HIHI) and the Mater Misericordiae University Hospital (MMUH) have announced a new partnership to facilitate innovation in healthcare in Ireland and improve patient care. The HIHI national team located in Cork, Dublin and Galway and the Mater Hospital will work together to deliver key programmes and activities to support the healthcare innovation ecosystem in Ireland. Projects will include working with clinical innovators at the hospital to create viable products and to develop pre-commercial prototypes and market ready products. Health Innovation Hub Ireland (HIHI) was established by the Department of Enterprise, Trade and Employment and the Department of Health, supported by Enterprise Ireland (EI) and the Health Service Executive (HSE) to drive collaboration between the health service and enterprise and is headquartered in University College Cork (UCC). The HIHI partnership facilitates access to the healthcare system through academic partners in its host institutions nationally in University College Cork (UCC), Munster Technological University (MTU), University of

Galway (NUIG), Trinity College Dublin (TCD) and the academic institution’s respective hospital groups namely the South/South West Hospital Group, the Dublin Midlands Hospital Group and the Saolta Healthcare Group. HIHI is delighted to welcome the Mater to this innovative network and marks the expansion of HIHI’s clinical and academic sites in Ireland. Working with enterprise, HIHI supports the development of new healthcare technologies, products, and services through its healthcare innovation pathway. It facilitates access to hospitals, primary care centres, community and other healthcare settings, for pilot and validation studies. HIHI’s remit is crucial for Irish companies as it provides an indepth knowledge of healthcare requirements and processes and provides access to Key Opinion Leaders (KOLs) in healthcare. Working with healthcare, HIHI works directly with healthcare professionals and those active in health provision nationally. HIHI supports the development of ideas from clinicians on the frontline into products and services through idea assessment and provides support with funding options, mentoring, as well as providing

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

The experience HIHI brings to this new partnership matches the innovative strides of the team at the Mater Hospital. In 2018, MMUH established the Pillar Centre for Transformative Healthcare offering a unique, flexible, interdisciplinary educational space for education, clinical research and healthcare innovation. The Pillar Centre for Transformative Healthcare exemplifies the vision of MMUH to be a leader in innovation of specialist services and healthcare transformation with a strong academic and research agenda.

The Med Tech Incubator Site at the Pillar Centre will ensure the continued growth of the Mater Hospital’s innovation programme and will act as a hub for ‘spin in companies’ and innovators to work together on innovation projects. The partnership with HIHI will facilitate the launch of this pioneering Medtech Incubator Hub in the MMUH and will increase its profile in Healthcare Medtech Innovation as well as spearheading a best practice model of design-led clinical innovation within the hospital. This will facilitate clear pathways for triage, development and commercialisation of these innovations- which is also the goal of the Health Innovation Hub, nationally.

In a recent development to continue the innovation journey at MMUH, an allocated space was designated within the Pillar Centre as a site for a proposed Medtech Incubator Hub. The partnership will also co-fund an appointment to lead the unit. To date a number of potentially viable commercial ideas have been developed by Mater staff through Medtech Innovation Sprints. The Pillar Centre is also committed to developing specialist postgraduate education in the medtech / device innovation space. The interaction

Prof Brendan Kinsley, Clinical Director at the Pillar Centre for Transformative Healthcare, welcomed the partnership, “This is an exciting development for the Mater Hospital and the Pillar Centre. We see the value that innovation brings to patient care and the support of HIHI is crucial as we develop the Med Tech Incubator Hub at the Pillar Centre. The co-funding of a full-time position to drive our collaboration will allow us to continuously strive to bring the best in innovation to a hospital setting.”

access to academic research expertise to develop solutions to everyday problems.

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58 News

Using Artificial Intelligence to Treat Kidney Disease Professor Donal Redden, Consultant Nephrologist at Galway University Hospital, Dr David Keane, Postdoctoral Researcher at the University of Galway, Dr Sarah Monahan, Senior House Officer in Nephrology at Galway University Hospital, and Dr Conor Judge, Consultant Nephrologist at Galway University Hospital

Innovation Fund who support these types of initiatives that will improve our healthcare system in a meaningful way for patients, staff and the public." Dr Howard Johnson, Clinical Director of the HSE National Health Intelligence Unit, added; "This project could pave the way for similar initiatives across other parts of our health services to use the vast amounts of available and unused data to support the delivery of high-quality, efficient, and effective health care." A team of clinicians and researchers from Galway are using Artificial Intelligence to transform how we treat patients with kidney disease The collaboration involves the Saolta University Health Care Group, HSE National Health Intelligence Unit, College of Medicine, Nursing, and Health Science, University of Galway, The National Renal Office, HSE Integrated Information Services, Insight Data Analytics, Health Innovation Hub Ireland, and eHealth Ireland. It has been funded by the Public Service Innovation Fund operated by the Department of Public Expenditure, NDP Delivery and Reform (DPENDR). Chronic Kidney Disease (CKD) is a progressive condition that affects approximately 10% of people

worldwide. Some patients with CKD progress to kidney failure requiring lifesaving treatments like dialysis or kidney transplant. The Kidney Disease Clinical Patient Management System (KDCPMS) is an electronic health record to manage the care of patients receiving dialysis or kidney transplant. One challenge faced by healthcare providers is extracting actionable information from large quantities of unstructured free text, such as clinical notes and outpatient letters, stored in the KDCPMS. This data in its current form is difficult to organise and use for making national decisions about kidney care in Ireland. Now, the renal AI project is using Artificial Intelligence Language Models to extract key structured information from the free-text clinical notes to inform national kidney disease strategy.

Dr Conor Judge, a consultant nephrologist at Galway University Hospitals and senior lecturer in Applied Clinical Data Analytics at the University of Galway, and Clinical Lead in Health Innovation Hub Ireland, is leading this transformative project.

Dr Steven Griffin, Manager, Health Innovation Hub Ireland, said; “The public service innovation fund plays a pivotal role in empowering those within our public service who are dedicated to the betterment of society. This collaboration harnesses clinical expertise, technical advancements, and a patientcentric approach to revolutionise the quality of life for some of our most vulnerable citizens. It exemplifies the transformative potential and imperative needed for lasting change with tangible benefits for renal patients and the healthcare system at large."

He expressed his excitement for the project, stating that "using Artificial Intelligence in this way will allow us to harness this rich data source to improve patient care in a way that has not been possible to date. We are grateful to the team in the Public Service

“This project will allow the National Renal Office to accurately measure key quality care parameters in the delivery of renal care nationally and help drive improvements in care” said the NRO Clinical Director, Professor George J. Mellotte.

different tools available that can support this effort, such as: ready-to-administer syringes and standardised drug concentrations.

syringes in relation to the different levels of resources available to hospitals across Europe.

The AI powered solution will ensure uniformity and clarity in health records. This information is now being used to compare the quality of Irish patient care to other European and international nephrology centres, a previously impossible task.

Use of Prefilled Syringes SIG The European Association of Hospital Pharmacists (EAHP) is publishing the Special Interest Group (SIG) Report on the Use of Prefilled Syringes in Intensive Care Units and Operating Theatres. Patient-safety lies at the heart of all representations made by the European Association of Hospital Pharmacists (EAHP) and its member associations.

Its importance for hospital pharmacy practice has also been manifested in a dedicated section of the European Statements of Hospital Pharmacy that among other things, emphasises that hospital pharmacists should help to decrease the risk of medication errors by disseminating evidence-based approaches to error reduction. There are many

JANUARY 2024 • HPN | HOSPITALPROFESSIONALNEWS.IE

The EAHP decided to investigate this topic further and created the SIG on the Use of Prefilled Syringes in Intensive Care Units and Operating Theatres, tasked with looking at the cost and benefits, as well as the viability of prefilled

We want to thank all the members of the SIG for their work, contributions, and efforts in preparing this report, and all individual pharmacists and other professionals who participated in the Survey that helped collect data for said report.

News 59 Ensuring ‘No Patient is Left Behind’ New research from the RCSI has highlighted continued shortcomings in fracture prevention services across Ireland as well as the urgent need to adequately fund and resource the implementation of a National Fracture Liaison Service. In its second annual report, the RCSI found that while improvements across a number of areas have been made, a number of regions across Ireland lack any sort of Fracture Liaison Service (FLS) infrastructure. As of September 2023, just 69% (11 out of 16) of all adult hospitals that manage trauma in Ireland have a FLS. This figure makes clear the need for a National Fracture Liaison Service. Not only would this benefit patients and offer improved health outcomes, but it is a costeffective prevention that would deliver long-term savings to the health service. Professor Frances Dockery, Joint Clinical Lead for the Fracture Liaison Service (FLS) Database, said:, “We are pleased to publish our second annual report on how patients in Ireland with fractures are being managed in order to

reduce future fracture risk. While great strides have been made in rolling out FLS across Ireland, there remains significant room for improvement and this year’s report underlines the need for our National FLS so that no patient is left behind. We welcome the HSE’s commitment to prioritise the FLS pathway for implementation in 2023/2024 and hope that all 16 adult trauma hospitals will soon be operating a fully resourced FLS.” This year, nine hospitals submitted data for inclusion in the Irish Fracture Liaison Service Database Annual Report 2023. Between them, they reported 3,195 non-hip fragility fractures in 2022. This figure represents just 33% of the expected number of non-hip fragility fractures attending hospitals in Ireland but is nonetheless an improvement on 2021. In the absence of a fully resourced National Fracture Liaison Service, no hospital successfully met each of the standards outlined in the International Osteoporosis Foundation’s Capture the Fracture best practice framework. Ireland is home to an ageing population with the incidence of

new fragility fractures each year estimated to be 32,000. This figure is expected to increase to 51,000 per year in the next ten years and is the highest in all EU countries as the population ages. A fragility fracture is defined as a broken bone sustained from a minor trip or bump. Such fractures can be extremely debilitating and can have a devastating impact on a person’s ability to live independently, which is why secondary fracture prevention is so important. Among the report’s key findings was that vertebral (spine) fractures need to be prioritised for case finding as these patients are at greatest risk of further fractures. Data from 2022 showed that just 26% of the expected number of vertebral fractures were identified nationally(1). This illustrates the need to develop a specific national strategy for case finding within this patient group. Additionally, the report identified a need for greater follow-up care with just 35% of patients recommended anti-osteoporosis medication (down from 53% in 2021). Only 11% of patients

were referred to start strength and balance training and just 5% started within 16 weeks of their fracture. This is despite the fact that these are recognised as critical interventions when it comes to reducing the risk of re-fracture and preventing future falls. Mr. Aaron Glynn, Joint Clinical Lead for the Fracture Liaison Service Database, said, “The 2023 fracture liaison service database report demonstrates the efforts being made at a national level to reduce the risk of avoidable fractures for patients. However, it is abundantly clear that real progress cannot be made until we have a fully funded and resourced National Fracture Liaison Service. The social and economic burden imposed by fragility fractures mandates that we move away from therapeutic nihilism toward a proven model for reducing their occurrence. Our recommendations clearly outline the steps needed to close the treatment gap and ensure patients across Ireland have access to quality proactive care. We urge decision-makers at all levels to review the report and act on the recommendations as a matter of priority.”

IRC Early Career Researcher of the Year Award Maynooth University congratulates Professor Aisling McMahon of the School of Law and Criminology on receiving the highly prestigious IRC Early Career Researcher of the Year Award for her work in health and intellectual property law. This national IRC Award recognises a current or previous IRC awardee, who is within eight years of award of their PhD, and who has demonstrated an exceptional level of achievement in their field at this stage in their career. Professor McMahon has led pioneering and internationally recognised research on the impact of intellectual property (IP) rights on people’s access to healthcare and on the development and delivery of health technologies. A 2020 article by Professor McMahon examining the impact of patent rights on which countries could access Covid-19 vaccines, medicines and diagnostics first, and on what terms, was cited as an information source for a UK House of Commons Briefing in November 2020. In 2022, she was awarded a highly prestigious European

Professor Aisling McMahon

Research Council Starting grant for the PatentsInHumans project. Professor McMahon’s research is especially focussed on the regulation of emerging healthtechnologies and biotechnologies, and the relationship between intellectual property law and bioethics in the context of health-related technologies. Maynooth University received a total of three Researcher Awards, including two commendations, and nine ‘Research Allies’ honours in last night’s ceremony, which recognises excellence and an exceptional track record in a field of research funded by the IRC. Accepting her award, Professor McMahon said, "Scientific research can have incredible benefits for human health. My research is driven by building understandings of the role that legal and regulatory mechanisms can play in fostering the

development of cutting-edge ethically responsible health technologies; and alongside this, developing understandings of how legal tools can facilitate and ensure equitable access to such health technologies for all those who need them. “To me, this award underlines the importance of this field of research. Children and young people in care, in particular

residential care, are seldom heard in the education space or in the space of research, and tend not to get many opportunities to research, discuss and analyse the issues affecting their lives. We need more research to understand how to better deliver care and other services for this population, and to learn from children and young people who have so much to offer the research space,” she said.

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60 Clinical R&D ABBVIE NAMED AS A 2023 BEST WORKPLACE IN PHARMA & HEALTHCARE BY GREAT PLACE TO WORK IRELAND Great Place To Work, the global authority on workplace culture, has named biopharmaceutical company AbbVie on their 2023 Best Workplaces in Pharma & Healthcare in Ireland list. This is the second consecutive year that AbbVie has appeared on this prestigious list and AbbVie is one of only 20 companies and organisations recognised. Ireland’s Best Workplaces in Pharma & Healthcare 2023 is an industry recognition compiled by Great Place to Work Ireland honouring organisations building great cultures in the pharma and healthcare industries. The recognition highlights listed companies as employers of choice in an increasingly competitive talent market. To be considered for Ireland’s Best Workplaces in Pharma & Healthcare in 2023, participating organisations are required to be certified as a Great Place to Work. AbbVie, which employs more than 2,600 people across six different Irish locations from Sligo to Cork, and Mayo to Dublin, was named as one of the Best Large Workplaces in Ireland at the Great Place to Work 2023 Awards earlier this year – the tenth consecutive year that the company has featured on the list. The company was also acknowledged as one of the Best Workplaces for Women in Ireland for the fifth year in a row and was

Pictured celebrating the announcement that AbbVie has made the 2023 Best Workplaces in Pharma & Healthcare in Ireland are AbbVie Citywest employees: (L-R) Pablo Lopez, Rachel Edwards, Blanaid O’Connell, and Karen Vickers

ranked number 4 on the World’s Best Workplaces list in November. Speaking about this most recent accolade, Gary O’Mahoney, HR Director for Ireland, said: “Being named as one of Ireland’s Best Workplaces in Pharma & Healthcare again this year is an incredible accomplishment for the company. It is a validation of our efforts to create an inclusive workplace that supports employee development and also empowers them to make a broader impact in the communities where they live and work. “I would like to thank colleagues across our six locations in Ireland for their commitment to our company culture and ongoing dedication to patients around the world,” he added. The Best Workplaces in Pharma & Healthcare list is published here: https://www.greatplacetowork.ie/ great-workplaces/best-workplaces-inpharma-healthcare/best-workplaces-inpharma-and-healthcare/

BEYONDBMI RAISES ¤1 MILLION IN SEED FUNDING TO TRANSFORM OBESITY TREATMENT Beyondbmi (www.beyondbmi.ie), a pioneering medically-led digital obesity clinic, has announced that it has closed a ¤1 million seed funding round, led by private investors and Enterprise Ireland. This brings to just over ¤1.5 million the total raised by the University College Dublin (UCD) spin-out company this year. The new funding will be used to further develop and expand Beyondbmi’s services. The latest funding round was supported by new and existing investors including; Mick Slein (Chairman of Robus), David O’Reilly, Paddy Dillion (Head of Corporate Finance in Grant

Thornton), Bill Walsh, John Purdy (Chairman of Ergo and Beyondbmi), among others, marking a significant milestone in the clinic’s mission to transform the landscape of obesity care.

Pictured (l-r) at UCD are Beyondbmi team members; Professor Alex Miras; Dr Harriet Treacy, CEO and co-founder; Professor Carel Le Roux and Dr Werd Al-Najim. (Credit: Maura Hickey)

Beyondbmi, which is headquartered at NovaUCD in Dublin, offers a unique approach to addressing obesity through personalised medical interventions, community support, and cuttingedge technology. The clinic’s platform has already made a substantial impact on the lives of its clients, referencing an average weight loss of 10% at Month 6, demonstrating the effectiveness of the clinic’s comprehensive, wraparound approach to obesity care.

She added, “This latest seed funding injection underscores the commitment of our investors to support Beyondbmi’s vision of providing accessible and effective obesity care that prioritises the well-being and quality of life of its clients. Beyondbmi also plans to expand operations to the UK in 2024, providing our innovative obesity care solutions to a broader international audience.”

A UCD School of Medicine spinout Beyondbmi was founded by medical doctor Dr Harriet Treacy and product designer Peter Lumley with support from senior team members including world-leading obesity scientists and clinicians, Professor Carel Le Roux and Dr Werd Al-Najim, UCD School of Medicine and UCD Conway Institute and Professor Alex Miras, Ulster University. Dr Harriet Treacy, CEO, Beyondbmi, said, “Beyondbmi’s mission goes beyond weight loss, it focuses on the significant health gains its clients experience. These improvements range from increased mobility, reduced reliance on blood pressure medications, and a return to more active and engaged lives with their families. We have seen, on average, 30% month-on-month growth in signups since we began trading at the end of 2022. But more important than that, it’s the stories of our amazing clients and our incredible community that has consolidated the extent of the impact that we are having on people’s lives.”

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The new funding will be used by the company to invest in its mobile app, to provide clients with more convenient access to their personalised obesity care plans and a supportive community, to hire additional staff to scale its B2B offering, and to expand its expert clinician team, bringing in more specialists to cater to the diverse needs of its growing community. Professor Alex Miras, Ulster University, a leading obesity expert in the field, emphasising the importance of Beyondbmi’s work said, “Everyday, I have clients telling me they have been made to feel that obesity is their fault. As an obesity researcher and clinician, I see the detrimental impact this message has had on their lives and overall health, oftentimes developing conditions as a result of untreated obesity such as high blood pressure, chronic knee and back pain and fertility issues. Beyondbmi is much more than just a digital obesity clinic, for many of our clients, it is the first time they have been really listened to and supported in managing this disease.”

61 THE NATIONAL IMMUNISATION ADVISORY COMMITTEE (NIAC) RECOMMENDS PASSIVE IMMUNISATION AND VACCINATION AGAINST RESPIRATORY SYNCYTIAL VIRUS (RSV) GSK Ireland have welcomed the announcement from the National Immunisation Advisory Committee (NIAC) recommending passive immunisation and vaccination against RSV to protect infants, children, and older adults. NIAC said “Given the high burden of RSV in older adults in Ireland, both to individuals and to the healthcare system, the introduction of RSV vaccination for those aged 65 or older has the potential to reduce associated morbidity and mortality and relieve pressure on the healthcare system during the busy winter season.” NIAC has also added, that in the “event of limited supply of vaccines for older adults, priority should be given to those of more advanced age, those with significant comorbidities and those living in long term care facilities for older adults as they are at the highest risk of severe RSV disease.” This recommendation further supports the use of Arexvy (Respiratory Syncytial Virus vaccine, recombinant adjuvanted), the first vaccine available in Ireland to protect older adults from LRTD caused by RSV. Arexvy showed 82.6% overall efficacy against RSV-LRTD (primary endpoint) with 94.6% efficacy in older adults with at least one underlying health condition of interest and 94.1% against severe disease (secondary endpoints). Dr. Patrick Mitchell, Associate Professor of Medicine and Consultant Respiratory Physician Trinity College Dublin and Tallaght University Hospital said: “Each year hospitals in Ireland see a significant increase in admissions caused by winter respiratory viruses including RSV. Reducing the burden of this virus is a key priority for healthcare professionals and I’m pleased that we have a recommendation from NIAC to help protect vulnerable older adults from RSV for the first time.” Eimear Caslin, General Manager, GSK Ireland, said: “The NIAC recommendation for an RSV vaccine is a significant milestone for patients in Ireland and will reduce the burden of this debilitating disease. RSV was one of the few main respiratory infectious diseases with no available vaccine. Vaccination enables people to live longer, healthier lives as well as strengthening our economy and

bolstering our health service. We look forward to working with the HSE and healthcare professionals to ensure those at risk of RSV infection can access it.” Eilis Ní Chaithnía, CEO, Asthma Society of Ireland, said: “Every winter, Ireland experiences sharp rises in hospital admissions among people with respiratory diseases. For older persons, the presence of asthma or COPD creates a higher risk of severe symptoms from an RSV infection. The Asthma Society of Ireland is pleased to see a recommendation for RSV vaccination in older adults and looks forward to this protection being offered to all at-risk people.” STELARA® (USTEKINUMAB) ONE-PRESS PRE-FILLED PEN, A NEW PATIENT CONTROLLED INJECTOR FOR INFLAMMATORY BOWEL DISEASE, IS NOW APPROVED FOR USE WITHIN IRELAND The Janssen Pharmaceutical Companies of Johnson & Johnson has announced that STELARA® (ustekinumab) One-Press, a single dose, patient controlled, pre-filled pen, has been approved for use within Ireland for patients with Inflammatory Bowel Disease (IBD). One-Press was designed for easy patient use, with a convenient, controllable injection pen that allows patients to control the injection speed. Ustekinumab is administered initially intravenously, and then as a subcutaneous injection every 12 weeks (or every eight weeks, based on clinician judgement) starting at week 8, which is one of the lowest dosing frequencies amongst biologics and small molecules in IBD. Dr Jane McCarthy, Consultant Gastroenterologist, Mercy University Hospital, Cork said, “The availability of a One-Press device for Irish patients living with Inflammatory Bowel Disease is a welcome development. Patients often struggle to administer treatments with conventional syringes, which can reduce treatment adherence and impact long term outcomes. The OnePress device alleviates this struggle by allowing patients to easily self-administer their ustekinumab treatment with a device that is both simple and intuitive to use. In doing so, Irish patients living with IBD can take more control over the management of their condition.” Data shows that for patients using the One-Press: • 98 percent of patients reported that they were satisfied or very satisfied with self-injection at Week 12 of use

• 97 percent of patients reported that the pre-filled pen is easy to use • 97 percent of patients liked being able to control the speed of injection The nature of the pre-filled pen also gave patients confidence when injecting, with 95 percent agreeing they could easily tell when their injection was finished. In addition, the hidden, protected needle may reduce patient anxiety around accidental injection. Efficacy and safety profile of ustekinumab in IBD The four year UNIFI long term extension (LTE) study looked at 205 adult patients with a history of moderately to severely active UC who achieved clinical response to intravenous ustekinumab, and randomised patients to ustekinumab 90 mg maintenance every eight weeks or every 12 weeks. Results showed that at Week 200, for the combined group (week eight and week 12), 58 percent of patients were in clinical remission, and 80 percent of patients were in clinical response. In the five-year IM-UNITI trial, using an intent-to-treat analysis of all patients with moderately to severely active CD randomised to ustekinumab at maintenance baseline, 34.4 percent receiving ustekinumab every eight weeks, and 28.7 percent receiving ustekinumab every 12 weeks were in clinical remission at Week 252. Corresponding remission rates among patients who entered the LTE were 54.9 percent and 45.2 percent.1 A final pooled safety analysis from six Phase 2/3 IBD studies included 2,575 patients treated with ustekinumab and 4,826 patientyears of follow-up. Data continue to support a well-established safety experience for ustekinumab in adult patients with moderately to severely active UC through four years, and in adult patients with moderately to severely active CD through five years. MSD IRELAND LAUNCHES NEW CAMPAIGN TO INFORM ADULTS ABOUT HPV AND CERVICAL CANCER MSD Ireland has this month launched a new disease awareness campaign aimed at educating people about HPV and cervical cancer. The campaign aims to inform adults about the disease and empower them with the information they need to make informed decisions about their personal health and to increase health literacy generally around the topic.

A new website has been launched as part of the campaign, available at hpv-info.ie. This public disease awareness campaign will include digital media and social media. The new campaign by MSD represents a timely initiative aligned to the Department of Health’s recently launched roadmap to eliminate HPV-related cervical cancer in Ireland by 2040 through vaccination, screening, and treatment.1 Increasing awareness levels of HPV, and its contribution to cervical cancer, and other HPV-related illnesses is increasingly important in the context of achieving this ambitious goal to eliminate cervical cancer. Adults are encouraged to avail of information from reputable sources online or to speak with their doctor, nurses, or pharmacist for more information on HPV prevention and cervical screening, should they have a concern. DUPIXENT® SIGNIFICANTLY REDUCED COPD EXACERBATIONS IN SECOND POSITIVE PHASE 3 TRIAL, ACCELERATING FDA SUBMISSION AND CONFIRMING POTENTIAL TO BECOME FIRST APPROVED BIOLOGIC FOR THIS SERIOUS DISEASE The second Dupixent® (dupilumab) investigational Phase 3 chronic obstructive pulmonary disease (COPD) trial (NOTUS) has shown that Dupixent significantly reduced (34%) exacerbations, confirming positive published results from the landmark Phase 3 BOREAS trial. The NOTUS trial also confirmed that treatment with Dupixent led to rapid and significant improvements in lung function by 12 weeks and were sustained at 52 weeks. The NOTUS trial evaluated the investigational use of Dupixent compared to placebo in adults currently on maximal standard-ofcare inhaled therapy (triple therapy) with uncontrolled COPD and evidence of type 2 inflammation (i.e., blood eosinophils ≥300 cells per μL). These results were from an interim analysis and, given the overwhelming positive efficacy of the primary endpoint, will be considered the primary analysis of the trial. Sanofi and Regeneron plan to submit the data from this replicate trial, along with positive results from the Phase 3 BOREAS trial, to the U.S. Food and Drug Administration (FDA) by the end of the year. The NOTUS trial included 935 adults who were current or former smokers aged 40 to 85 years and randomized to receive Dupixent (n=470) or placebo (n=465), which was added to maximal standardof-care inhaled therapy. Patients receiving Dupixent compared to placebo experienced:

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62 Clinical R&D • 34% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p=0.0002), the primary endpoint. • Improved lung function from baseline by 139 mL at 12 weeks compared to 57 mL for placebo (p=0.0001), with the benefit versus placebo sustained at week 52 (115 mL for Dupixent versus 54 mL for placebo, p=0.0182), both of which were key secondary endpoints. The safety results were generally consistent with the known safety profile of Dupixent in its approved indications. Overall rates of adverse events (AE) were 67% for Dupixent and 66% for placebo. AEs more commonly observed with Dupixent (≥5% and ≥1% imbalance) compared to placebo included COVID-19 (9.4% Dupixent, 8.2% placebo), nasopharyngitis (6.2% Dupixent, 5.2% placebo), and headache (7.5% Dupixent, 6.5% placebo). AEs more commonly observed with placebo compared to Dupixent included COPD (7.8% placebo, 4.9% Dupixent). AEs leading to deaths were 2.6% for Dupixent and 1.5% for placebo. Detailed results from the NOTUS trial are planned for presentation at a future scientific forum. The efficacy results in NOTUS were consistent with the previously announced results in BOREAS. BOREAS results showed: • 30% reduction in moderate or severe acute COPD exacerbations over 52 weeks (p=0.0005), the primary endpoint. • Improved lung function from baseline by 160 mL at 12 weeks compared to 77 mL for placebo (p<0.0001), with the benefit versus placebo sustained through week 52 (p=0.0003). The safety results in NOTUS were also consistent with those previously announced in BOREAS. Overall rates of AEs in BOREAS were 77% for Dupixent and 76% for placebo. AEs more commonly observed with Dupixent compared to placebo included headache (8.1% Dupixent, 6.8% placebo), diarrhea (5.3% Dupixent, 3.6% placebo) and back pain (5.1% Dupixent, 3.4% placebo). AEs more commonly observed with placebo compared to Dupixent included upper respiratory tract infection (9.8% placebo, 7.9% Dupixent), hypertension (6.0% placebo, 3.6% Dupixent) and COVID-19 (5.7% placebo, 4.1% Dupixent). AEs leading to deaths were 1.5% for Dupixent and 1.7% for placebo. The European Medicines Agency is reviewing Sanofi and Regeneron’s

application for Dupixent for the treatment of uncontrolled COPD with type 2 inflammation; this application is based on results from the BOREAS trial. Discussions with other regulatory authorities around the world are ongoing. The safety and efficacy of Dupixent in COPD are currently under clinical investigation and have not been evaluated by any regulatory authority. JANSSEN ANNOUNCES APPROVAL OF ERLEADA® (APALUTAMIDE), THE FIRST-AND-ONLY BRANDED NOVEL HORMONAL THERAPY WITH ONCE-DAILY, SINGLE-TABLET OPTION NOW AVAILABLE IN IRELAND Janssen, the Pharmaceutical Companies of Johnson & Johnson has announced that an additional tablet strength of ERLEADA® (apalutamide) has been approved for use within Ireland. The 240 mg tablet formulation is approved for the same indications as the existing 60 mg strength, that is, adult men with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease, and for adult men with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).[i] This marks the first approval of a branded novel hormonal therapy (NHT) in a once-daily, single tablet formulation within the European Union.[ii],[iii],[iv] Professor John McCaffrey, Consultant Medical Oncologist, Mater Misericordiae University Hospital said “Non-adherence rates across oral prostate cancer treatments range from 25% to 51%[v] which is as much as every second patient. The ability to offer a novel hormonal therapy with a once-daily single-tablet dose can help positively address nonadherence rates in appropriate patients. The availability of this treatment represents a significant advancement for Irish patients offering greater convenience and the potential to improve outcomes.” Inadequate adherence to oral therapies has resulted in poor clinical outcomes. Mean nonadherence rates of 25 to 51 percent have been reported in prostate cancer patients prescribed oral therapies, with higher rates in older patients. The reasons for non-adherence are multi-factorial but may include complex dosing schedules, food requirements and sheer volume of concomitant medications. NHTs have helped revolutionise outcomes for patients with

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prostate cancer, demonstrating improvements in overall survival and delaying disease progression without compromising on quality of life.[vi],[vii] To date, published results on apalutamide include data from more than 2,000 patients across Phase 3 clinical studies. Apalutamide has shown a statistically significant improvement in overall survival (OS) with a generally well-tolerated safety profile in both approved indications of mHSPC (Phase 3 TITAN study) and high-risk nonmetastatic castration-resistant prostate cancer or nmCRPC (Phase 3 SPARTAN study). NEW MODEL OF CARE FOR VASCULAR SURGERY LAUNCHED AT RCSI A new model of care for vascular surgery has been launched today by the National Clinical Programme in Surgery (NCPS), a collaboration between the HSE and RCSI. The model of care, launched during RCSI’s annual Millin Meeting, outlines the service needs of the population for vascular surgery services and defines a model of care delivery that is accessible, timely and of high quality. It sets out recommendations to enable delivery of services of the highest quality over the next five to ten years. These include the resourcing of centralised services both in terms of staffing and facilities. Key to workforce expansion is the development of new nursing roles with specialist training and an extended scope of practice. The model of care also highlights the importance of establishing a National Vascular Registry to monitor and improve the quality of services and to record all implants. The document also advocates for a national screening programme for Abdominal Aortic Aneurysms in line with the UK and most European nations, as well as reinforcing some of the preventative measures that people can take to promote their vascular health such as smoking cessation, exercise and weight control. In developing this model of care, the complexity and multisystem nature of vascular disease and the necessity for multidisciplinary specialist input in the care of this cohort of patients were highlighted. The burden of vascular disease experienced by patients with diabetes was specifically addressed as an area of increasing importance given our aging population. Mr Martin Feeley, National Clinical Advisor for Vascular Surgery

(NCPS), said: “Launching this model of care is a milestone for vascular surgery. Irish Vascular surgeons are very keen to proceed with the implementation of these recommendations. The NCPS is grateful to all those who contributed to this work and in particular to the Irish Vascular Society.” Ms Mary Barry, Chair of the Irish Vascular Society, said: “We are delighted to introduce the Vascular Surgery Model of Care which represents our commitment to delivering better care for patients in Ireland”. The aim of the National Clinical Programme in Surgery (NCPS) is to provide a framework for the delivery of safer, more timely, accessible, more cost-effective and efficient care for all surgical patients. Professor Deborah McNamara, RCSI Vice-President and co-lead of the National Clinical Programme in Surgery, said: “This model of care will support the delivery of excellence in vascular surgical care. Through the National Clinical Programme in Surgery, RCSI collaborates with the HSE to drive improvements in policy and practice for the benefit of patients.” The model of care can be downloaded from publications section at: https://www.rcsi.com/ surgery/practice/national-clinicalprogrammes/surgery VHI ANNOUNCES THE EXPANSION OF VHI 360 HEALTH CENTRE NETWORK Vhi has announced the expansion of the Vhi 360 Health Centre network following the redevelopment of the Vhi SwiftCare Clinic in Swords. Vhi 360 Health Centre Swords now offers five additional clinical rooms, an improved member experience and access to a multi-disciplinary team of clinicians, who collaborate to deliver the best solution for members health needs. This year has seen a significant rise in the number of members who have accessed Vhi’s Health & Wellbeing services which include Vhi 360 Health Centres, the Clinical Call Centre, Digital platforms, and Hospital@Home. By September of this year Vhi’s Health and Wellbeing had supported members through over 420,000 healthcare interactions for a wide variety of healthcare needs, an increase of 33% from September 2022. This includes 120,000 healthcare interactions with members in Vhi 360 Health Centres in Dublin in Carrickmines and Swords, Limerick and Cork, an increase of 40%. Across these facilities, members availed of Urgent Care services including dental, orthopaedics,

63 Melbourne Hospital and Princess Margaret Paediatric Hospital in Perth, where he expanded his vast expertise and knowledge in emergency nursing. After completing a Postgraduate Diploma in Emergency Nursing at the University of Galway in 2009, Eóin took up the role of Clinical Nurse Facilitator in the Emergency Department at UHG until being appointed to Assistant Director of Nursing in 2018. During that time, he also taught Basic Life Support (BLS) and Advanced Cardiac Life Support (ACLS) skills as well as Trauma Nursing Core Course (TNCC) to Emergency Department Nurses across Ireland and the UK. Suzanne Bennett, Clinic Manager, Vhi 360 Health Centre Swords, Michele Tair, Chief Operations Officer, Vhi Health & Wellbeing and Dr Lynda Keavney, Chief Clinical Officer, Vhi Health & Wellbeing, Vhi 360 Health Centre Swords wound care and Planned Care Services including paediatrics, physiotherapy, dermatology, and diagnostics including MRI, X-Ray, and Ultrasound. Vhi also offers a digital and phone-based Health and Wellbeing services, enabling nationwide access to Vhi care that includes Vhi’s Online GP, Vhi’s Clinical Call Centre, NurseLine for support during a medical event or with day-to-day medical queries, as well as access to a suite of online health services including dieticians and physiotherapy. As of September, there were 220,000 interactions with members across these services, an increase of 28% on this time last year. Anne O’ Connor, Managing Director of Vhi Health & Wellbeing said, “At Vhi we want to support our members to stay well through our range of Wellness and Health Promotion services and give them access to high quality effective health services as needed. This year we are seeing an increase right across all our healthcare services with growing demand from members for both urgent and planned care. Following the redevelopment of our clinic in Swords we are now even better placed to respond to the everincreasing demand for care among our members.

which are now a hugely important and well-established part of the healthcare landscape. Our Vhi 360 Health Centre in Swords is a key component of our healthcare offering and we are glad to be able to offer increased capacity and an improved member experience.” Vhi 360 Health Centre Swords is open 7 days a week, 365 days a year from 8am to 9pm and offers a walk-in service for urgent minor injuries and illness. For more information go to Vhi.ie/360health. Vhi 360 Health Centre Swords is conveniently located in the Airside Retail Park.

In September 2021, following an extensive career at UHG, Eóin took up the role of candidate Advanced Nurse Practitioner at Roscommon Injury Unit. He recently graduated with an Honours Masters Degree in Advanced Nursing Practice which permitted him to enter the nursing register as an Advanced Nurse Practitioner. PORTIUNCULA UNIVERSITY HOSPITAL’S EUROPEAN ACCREDITATION Portiuncula University Hospital (PUH) has recently received European accreditation for the Echocardiography Department by the European Society of Cardiology (ESC) following a process of quality standards and improvements.

ROSCOMMON INJURY UNIT APPOINTS NEW REGISTERED ADVANCED NURSE PRACTITIONER IN EMERGENCY Roscommon University Hospital is delighted to announce that Eoin McGinn has recently been appointed as Registered Advanced Nurse Practitioner (RANP) in Emergency Nursing at Roscommon Injury Unit.

From left, Claire Mc Dermott, Chief II Cardiac Physiologist; Professor Aidan Flynn, Consultant Cardiologist; James Keane, Hospital Manager and Dr Núria Farre, Consultant Cardiologist

The European Association of Cardiovascular Imaging (EACVI) established a European Echocardiogram standard in laboratory practices and patient care. The aim of laboratory accreditation is to raise quality standards of practice and equipment across Europe in a uniform manner. It is also designed to be used as an educational tool to improve the overall quality of Cardiac Investigation departments. Portiuncula University Hospital is the third Hospital in the country to be accredited by the European Association of Cardiovascular Imaging. The cardiac Investigations Department provides a variety of non-invasive tests such as ECG, blood pressure, cardiac rhythm monitoring, exercise stress tests and echocardiography. Last year the department carried out 3,200 echocardiograms; a type of ultrasound for the heart used to aid in the diagnosis of a variety of cardiac disorders and to assess treatments for heart conditions. “This accreditation gives great confidence to patients knowing they are attending a department that is performing their echocardiograms to the highest standards," said Professor Aidan Flynn, Consultant Cardiologist. It also demonstrates our commitment to lifelong learning and knowledge expansion. The team's dedication to improving our service delivery has been incredible, and we are now lucky enough to be using the most advanced state-of-the-art echocardiography technology in our department.” For more information about the accreditation visit http://www. escardio.org/Education/CareerDevelopment/Accreditation/ EACVI-Laboratory-accreditation/ Accredited-Laboratories

RANPs are the highest level of clinical experts in the nursing profession in Ireland today and are transforming services for patients through an expanded scope of practice, greater clinical autonomy and decision-making.

“In 2023 Vhi continued to expand the range of multidisciplinary health services through the launch of Vhi Midwife Support Service, Women’s Health Clinic and Dermatology service and the ongoing development of other services including a Paediatric service , Sports, Exercise and Musculoskeletal Clinic and Positive Mind Programme.

Eóin, a native of Tuam in County Galway, began his nursing career at Cork University Hospital before moving to London to work as an Emergency Nurse at the King George Hospital. After two years in London, Eóin returned to Ireland to continue his career as an Emergency Nurse in the Emergency Department at University Hospital Galway (UHG).

Anne O’ Connor continued “Vhi has a long history of innovating in healthcare in Ireland, we introduced urgent care clinics

In 2003 Eóin took a career break to visit Australia and follow the Rugby World Cup. While there, he got the opportunity to work at The Royal

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Effectiveness of golimumab in rheumatology patients after failure of initial TNFαi therapy - A pooled data analysis.1 Simponi, in combination with methotrexate (MTX), is indicated for:2

• the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate.

• the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX

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patients with risk factors for skin cancer. Heart Failure: Golimumab should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and golimumab must be discontinued in patients who develop new or worsening symptoms of heart failure. Some cases had a fatal outcome. Neurological events: Use of anti-TNF therapy, including golimumab, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. Discontinuation of golimumab should be considered if these disorders develop. Carefully consider the benefits and risks before initiation of therapy in patients with a history of demyelinating disorders. Surgery: Patients requiring surgery whilst on golimumab therapy should be closely monitored for infections. Autoimmune processes: If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with golimumab and is positive for antibodies against double-stranded DNA, treatment should be discontinued. Haematological reactions: There have been post-marketing reports of pancytopenia, leukopenia, neutropenia, agranulocytosis, aplastic anaemia, and thrombocytopaenia in patients receiving TNF-blockers, including golimumab. Patients should be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation should be considered in patients with significant haematologic abnormalities. Vaccinations/therapeutic infectious agents: It is recommended that live vaccines or any therapeutic infectious agents should not be given concurrently. Allergic reactions: If an anaphylactic reaction or other serious allergic reaction occurs, administration of golimumab should be discontinued immediately, and suitable treatment initiated. The needle cover of the pre-filled pen contains latex and may cause allergic reactions in those sensitive to latex. Special populations: Older patients (≥ 65 years): Adverse events, serious adverse events and serious infections in patients aged ≥65 were comparable to those observed in younger patients. However, caution should be exercised when treating the elderly, particular attention should be paid to infections. There were no patients age 45 and over in the nr-Axial SpA study. Paediatric patients (<18 years): Vaccinations: it is recommended that prior to initiating golimumab therapy, paediatric patients be brought up to date with all immunisations in agreement with current immunisation guidelines. Excipients: Simponi contains sorbitol (E420). In patients with rare hereditary problems of fructose intolerance, the additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. INTERACTIONS Combination of golimumab and other biological therapeutics used to treat the same conditions as golimumab, including anakinra and abatacept is not recommended. PREGNANCY AND LACTATION Administration of golimumab is not recommended during pregnancy or breast-feeding. Women of childbearing potential should use adequate contraception and continue its use for at least 6 months after the last golimumab treatment. SIDE EFFECTS Refer to SmPC for complete information on side effects Very Common (≥ 1/10): upper respiratory tract infection; Common (≥1/100): bacterial infections, lower respiratory tract infections, viral infections, bronchitis, sinusitis, superficial fungal infections, abscess, leukopenia (including neutropenia), anaemia, allergic reactions, autoantibody positive, depression, insomnia, dizziness, headache, paraesthesia, hypertension, asthma and related symptoms, dyspepsia, gastrointestinal and abdominal pain, nausea, gastrointestinal inflammatory disorders, stomatitis, alanine aminotransferase increased, aspartate aminotransferase increased, pruritus, rash, alopecia, dermatitis, pyrexia, asthenia, injection site reaction, chest discomfort, bone fractures were reported. Serious, including fatal adverse events have been reported including septic shock, lymphoma, leukaemia, melanoma, Merkel cell carcinoma, hepatosplenic T-cell lymphoma*, leukopenia, thrombocytopaenia, pancytopaenia, aplastic anaemia, agranulocytosis, serious systemic hypersensitivity reactions (including anaphylactic reaction), skin exfoliation, vasculitis (systemic), sarcoidosis, demyelinating disorders, congestive heart failure, arrhythmia, ischaemic coronary artery disease, thrombosis, interstitial lung disease and lupus-like syndrome. * Observed with other TNF-blocking agents. Paediatric population: pJIA: The safety of golimumab has been studied in a phase III study of 173 pJIA patients from 2 to 17 years of age. The average follow-up was approximately two years. In this study, the type and frequency of adverse events reported were generally similar to those seen in adult RA studies. PACKAGE QUANTITIES 1 x 50 mg pre-filled pen containing 50 mg of golimumab in 0.5 ml solution for injection 1 x 50 mg pre-filled syringe containing 50 mg of golimumab in 0.5 ml solution for injection 1 x 100 mg pre-filled pen containing 100 mg of golimumab in 1 ml solution for injection Legal Category: Prescription Only Medicine. Marketing Authorisation Number 50 mg Pre-filled Pen EU/1/09/546/001 50 mg Pre-filled Syringe EU/1/09/546/003 100 mg Pre-filled Pen EU/1/09/546/005 Marketing Authorisation Holder Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands Date of Revision of Text: February 2019 © Merck Sharp & Dohme Ireland (Human Health) Limited 2019. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. X-083G-Feb2019. Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie Adverse events should also be reported to MSD (Tel: 01-299 8700) References 1. Govoni M, et al. Poster presented at the American College of Rheumatology; Philadelphia, PA, USA; November 10-14, 2022. Abstract available at Arthritis Rheumatol. 2022; 74 (suppl 9). 2. Simponi Summary of Product Characteristics Feb 2023

Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland

IE-GOL-00230 Date of Preparation: July 2023

Simponi 50 mg, 100 mg Solution for Injection in pre-filled pen Simponi 50 mg Solution for Injection in pre-filled syringe (golimumab) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing PRESENTATION Simponi 50 mg solution for injection in pre-filled pen Simponi 50 mg solution for injection in pre-filled syringe Simponi 100 mg solution for injection in pre-filled pen INDICATIONS Rheumatoid Arthritis (RA): Simponi, in combination with methotrexate (MTX), is indicated for: the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate; the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX. Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function; Psoriatic Arthritis (PsA): Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive PsA in adults when the response to DMARD therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function. Ankylosing Spondylitis (AS): Simponi is indicated for the treatment of severe, active AS in adults who have responded inadequately to conventional therapy. Non-radiographic axial spondyloarthritis (nr-Axial SpA): Simponi is indicated for the treatment of severe, active nr-Axial SpA who have had an inadequate response to or are intolerant to NSAIDs. Ulcerative colitis (UC): Simponi is indicated for treatment of moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. Polyarticular juvenile idiopathic arthritis (pJIA): Simponi 50mg in combination with MTX is indicated for the treatment of polyarticular juvenile idiopathic arthritis in children with a body weight of at least 40 kg, who have responded inadequately to previous therapy with MTX. DOSAGE AND ADMINISTRATION Simponi should be injected subcutaneously. Treatment should be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of RA, PsA, AS, nr-Axial SpA, UC or pJIA. After proper training in subcutaneous injection technique, patients may self-inject, if their physician deems it appropriate. RA: Simponi 50 mg given once a month, on the same date each month, concomitantly with MTX. PsA: Simponi 50 mg given once a month, on the same date each month, alone or in combination with MTX. AS and nr-Axial SpA: Simponi 50 mg given once a month, on the same date each month. Clinical response is usually achieved within 12-14 weeks of treatment (3 or 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period. In patients weighing more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once a month may be considered, taking into account the increased risk of certain serious adverse reactions with the 100 mg dose compared with the 50 mg dose. UC: Patients weighing < 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2. Patients who have an adequate response should receive 50 mg at week 6 and every 4 weeks thereafter. Patients who have an inadequate response may benefit from continuing with 100 mg at week 6 and every 4 weeks thereafter. Patients weighing ≥ 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks. During maintenance treatment, corticosteroids may be tapered, following clinical practice guidelines. Clinical response is usually achieved within 12-14 weeks of treatment (after 4 doses). pJIA: Simponi 50 mg administered once a month, on the same date each month, for children with a body weight of at least 40 kg. Clinical response is usually achieved within 12 to 14 weeks of treatment (after 3-4 doses). Missed dose: If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient remembers. The patient should be instructed not to inject a double dose. Older patients (≥ 65 years): no dose adjustment required. Paediatric patients (<18 years): For indications other than pJIA, Simponi is not recommended. Patients with renal and hepatic impairment: Simponi is not recommended. CONTRAINDICATIONS Patients with a hypersensitivity to golimumab or any of the excipients; Patients with active tuberculosis (TB) or other severe infection such as sepsis and opportunistic infections; patients with moderate or severe heart failure (NYHA class III/IV). PRECAUTIONS AND WARNINGS Infections: Patients must be monitored closely for infection before, during and for 5 months after cessation of treatment. Exercise caution when considering golimumab in patients with chronic infection or a history of recurrent infection including use of concomitant immunosuppressive therapy. Golimumab should not be given to patients with clinically important active infection. Patients should be advised of the potential risk factors. Bacterial infections (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported. The invasive fungal infection should be suspected if they develop a serious systemic illness. There was a greater incidence of serious infections, including opportunistic infections and TB, in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. Serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infection. There have been reports of active TB in patients receiving golimumab, including patients previously treated for latent TB. Patients should be evaluated for active or latent TB before golimumab treatment. All such tests should be recorded on the Patient Reminder Card provided with the product. If active TB is diagnosed, treatment with golimumab should not be initiated. If latent TB is diagnosed, treatment with anti-TB therapy must be initiated before initiation of golimumab. Patients on golimumab should be monitored closely for signs and symptoms of active TB and advised to seek medical advice if signs and/or symptoms of TB appear. Hepatitis B (HBV) reactivation: Reactivation of HBV occurred in patients receiving golimumab who were chronic carriers. Some cases had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with golimumab Malignancies and lymphoproliferative disorders: Caution is advised when considering golimumab treatment in patients with history of malignancy or continuing treatment in patients who develop a malignancy, additional caution should be exercised in patients with increased risk for malignancy due to heavy smoking. A risk for the development of malignancies in children and adolescents cannot be excluded. Rare cases, usually fatal, of hepatosplenic T-cell lymphoma (HSTCL) have been reported, the majority of cases occurred in adolescent and young males nearly all on concomitant treatment with azathioprine (AZA) or 6-mercaptopurine (6–MP). The potential risk with the combination of AZA or 6-MP and golimumab should be carefully considered. A risk for the development for HSTCL in patients treated with TNF-blockers cannot be excluded. Colon dysplasia/carcinoma - Screen for dysplasia in all patients with UC who are at increased risk or had a prior history for dysplasia or colon carcinoma. In newly diagnosed dysplasia patients the risks and benefits of continued golimumab use should be carefully assessed. Melanoma and Merkel cell carcinoma (all TNF-blocking agents including golimumab) have been reported, periodic skin examination is recommended, particularly for