Clinical R&D

DARZALEX® (DARATUMUMAB)

APPROVED FOR REIMBURSEMENT IN IRELAND

Janssen, the Pharmaceutical Companies of Johnson & Johnson has announced Darzalex® (daratumumab) in combination with bortezomib, thalidomide and dexamethasone (VTd) has been granted reimbursement in Ireland for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT). The announcement follows EC approval of daratumumab based on results from Part one of the Phase 3 CASSIOPEIA (MMY3006) study, published in The Lancet5 in June 2019 and presented at the 2019 American Society of Clinical Oncology (ASCO) Meeting. Professor Philip Murphy, Consultant Haematologist, Beaumont Hospital said, “For Irish patients newly diagnosed with multiple myeloma, the importance of early intervention with effective first-line treatments to maximise response cannot be emphasised enough. Improvements in the standard of care to provide patients with valuable extra time are vital. Data from the CASSIOPEIA study demonstrates that the addition of daratumumab in combination with VTd can lead to deep remissions and prolong PFS.” Dr Thorsten Giesecke, General Manager, Commercial Business, Janssen Sciences Ireland UC, said, “Janssen is committed to providing access for patients to daratumumab in earlier disease stages of multiple myeloma, a type of blood cancer that can have a devastating impact on the lives of those affected. Every year in Ireland about 350 people are diagnosed with this condition, and today’s reimbursement provides those who are newly diagnosed and transplant eligible, with a long-awaited additional frontline therapy.”6 The Phase 3 CASSIOPEIA trial is a two-part study. Results from this first part of the trial showed that after consolidation, the stringent complete response (sCR) rate was significantly higher in the daratumumab-VTd arm (29 percent) compared to VTd alone (20 percent) (Odds Ratio [OR] = 1.60; 95 percent confidence interval [CI], 1.21-2.12; P<0.0010).2 At a median follow-up of 18.8 months, PFS was significantly improved in the daratumumabVTd group compared to VTd alone (Hazard Ratio [HR] = 0.47; 95 percent CI, 0.33-0.67; P<0.0001), and the median PFS was not reached in either arm.2 The addition of daratumumab to VTd resulted in an 18-month PFS rate of 93 percent compared to 85 percent for VTd alone.2 The most common (≥10%) Grade 3/4 treatment-emergent adverse events (TEAEs) for daratumumabVTd and VTd, respectively, were neutropenia (28 percent vs. 15 percent), lymphopenia (17 percent vs. 10 percent), stomatitis (13 percent vs. 16 percent) and thrombocytopenia (11 percent vs. 7 percent).2 In the daratumumabVTd combination arm, infusionrelated reactions occurred in 35 percent of patients.2

91% OF IRISH ADULTS SUFFER FROM BACK PAIN

Minister of State, Patrick O’Donovan, T.D., officially opened the new Spine Excellence clinic in Limerick, a collaboration between Mater Private Network and the Poynton Spine Care Institute, bringing advanced spine care directly to patients in Limerick and Munster. The new clinic is a centre of excellence delivering comprehensive assessment, diagnosis, treatment and rehabilitation of spine conditions. Spinal pain is a complex and multifactorial condition that is often poorly understood, incorrectly assessed, and inadequately treated. At Spine Excellence, the expert team have a deep understanding of all aspects of spinal pathology and work with patients to develop a bespoke plan. The extent to which Irish people suffer from back pain was made clear in a survey commissioned in conjunction with the official opening of the clinic. Conducted by Bounce Insights for Mater Private Network, the survey among 500 Irish adults (28% of whom were from the Munster region) found that 91% of respondents suffered from back pain, while 46% reported missing either work or college because of their pain. Furthermore, 61% percent of respondents said they have visited their GP as a result of back pain and 53% said that their pain has impacted personal time with family and friends.

Minister of State, Patrick O’Donovan TD with Spine Excellence Clinical Director and leading Irish spine surgeon, Mr. Ashley Poynton, David Slevin, Deputy Chief Executive of Mater Private Network Spine Excellence Clinical Director and leading Irish spine surgeon, Mr. Ashley Poynton, said, “I am incredibly proud of our team here at Spine Excellence. They will be able deliver a uniquely comprehensive approach to spine care in a stateof-the-art facility and rapid access to the Mater Private Network high tech spinal facilities in the Cork and Dublin hospitals, when needed. Our team has a broad and deep knowledge of spinal pathology from highly complex surgical cases to the most challenging rehabilitation patients and everything in between. “Most spinal pain can be treated successfully by regaining movement, flexibility, and strength, and building confidence in functional movement and exercise. While many people with spinal pain do not need any intervention other than rehabilitation, others may have underlying conditions that require deeper intervention, up to and including surgery. At Spine Excellence in Limerick, we have assembled an expert team, from specialist consultants and surgeons to spine expert physiotherapists to deal with all eventualities and all spinal pathologies. “Our philosophy is centred around the patient understanding the nature of the problem and building confidence in their own ability to recover.”

David Slevin, Deputy Chief Executive of Mater Private Network, said, “Mater Private Network is delighted to deepen our collaboration with the Poynton Spine Care Institute through the establishment of Spine Excellence in Limerick. Along with our hospitals in Cork and Dublin, we already have a presence in Limerick as the operator of the Mid-Western Radiation Oncology Centre at University Hospital Limerick. We understand how important it is to make best in class healthcare services more accessible to patients in the region. We are delighted to be part of Spine Excellence in Limerick with outstanding surgeons Mr. Ashley Poynton, Mr. Deb Roy, Mr. Islam Gawish along with the expert team.”

GSK ON BEHALF OF VIIV

HEALTHCARE LAUNCHES VOCABRIA  AND REKAMBYS  IN IRELAND

GSK Ireland on behalf of ViiV Healthcare is pleased to announce that eligible people living with Human Immunodeficiency Virus (HIV) in Ireland now have access to Vocabria (cabotegravir longacting injection) developed by ViiV Healthcare in combination with Rekambys (rilpivirine long-acting injection) developed by Janssen Sciences Ireland UC (Janssen), one of the Janssen Pharmaceutical Companies of Johnson & Johnson. Vocabria and Rekambys is indicated for the treatment of HIV type 1 (HIV-1) infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL), on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the non-nucleoside reverse transcriptase inhibitor (NNRTI) and integrase inhibitor (INI) class.1 This marks the first time that people living with HIV in Ireland can access a complete, longacting regimen once every two-months. This could reduce the number of days receiving treatment from 365 to 6 per year, when on the continuation injection phase of treatment. Professor Sam McConkey, Head of the Department of International Health and Tropical Medicine at the Royal College of Surgeons said: “Over the last 20 years great progress has been made in developing effective treatments for HIV that can suppress the virus in the body to undetectable levels, however until now it has required daily treatment. The introduction of a long-acting injectable treatment means that eligible people living with HIV will only need to be treated every two months, rather than every day. This approach has the potential to help lessen the burden of treatment and reduce the worry and stigma that comes with having to take treatments daily. We have used IM cabotegravir in the context of a phase III clinical trial in Ireland

and the patients in the trial were delighted to participate.” Dr Nneka Nwokolo, Head of Global Patient Affairs at ViiV Healthcare and honorary consultant in sexual health and HIV medicine said: “At ViiV Healthcare, our mission is to ensure that no one living with HIV is left behind and we recognise that there are still unmet needs in both the choice of medication they take, and how often they take it. We understand that no medicine works for every individual living with HIV, so we are committed to offering innovative choices that help address their evolving needs. We are delighted that the first and only complete long-acting injectable HIV medicine is now available in Ireland, allowing us to focus on the people living with the condition and provide them with treatment options that remove the need for regular daily HIV tablets.” Outlining the need for a less frequent dosing regimen, the largest global HIV patient-reported outcomes study to-date conducted by ViiV Healthcare, Positive Perspectives Wave 2, which included 50 Irish participants, found that when asked about their treatment aspirations and attitudes towards innovative medications, 55% (n=1306/2389) of participants said they would prefer not having to take medication every day, as long as their HIV stays suppressed.2 In addition, 58% (n=1394/2389) noted that taking daily HIV medication acts as a constant reminder of HIV in their lives, while up to 38% (n=906/2389) of participants reported anxiety around the fact that taking daily treatment could increase the chances of revealing their HIV status to others.3

Stephen O’Hare, Executive Director at HIV Ireland said: “HIV Ireland welcomes the option of longacting injectable antiretroviral treatment for people living with HIV. For those eligible, this choice of treatment could be game changing for people who struggle with their current regimens, by eliminating the daily pill burden. The impact of this new treatment option could greatly improve adherence and reduce the burden for marginalised and harder-to-reach communities who may prefer the 2-monthly regimen to a daily oral pill.”

SANOFI-GSK NEXTGENERATION COVID-19 BOOSTER DELIVERS STRONG IMMUNE RESPONSE AGAINST VARIANTS OF CONCERN, INCLUDING OMICRON

Sanofi has reported data from two trials, VAT02 Cohort 2 and COVIBOOST VAT013, conducted with its new next-generation COVID-19 booster vaccine candidate modelled on the Beta variant antigen and including GSK’s pandemic adjuvant. In the Phase 3 VAT02 Cohort 2 study, the Sanofi-GSK nextgeneration vaccine candidate induced (at day 15 postimmunization) a significant boost in antibody titers above baseline against multiple variants of concern (15-fold increase against D614 parent virus, 30-fold increase against Beta strain) in adults previously primed with mRNA COVID-19 vaccines. In particular against Omicron, preliminary data show a 40-fold increase against BA.1. The SanofiGSK next-generation booster candidate generated double the number of neutralizing antibodies against Omicron BA.1 and BA.2 compared to the D614-based (original parent virus) booster. In parallel, the independent COVIBOOST (VAT013) study conducted by the Assistance Publique – Hôpitaux de Paris (AP-HP) demonstrated that, following primary vaccination with two doses of Pfizer-BioNTech’s Comirnaty vaccine, the SanofiGSK next-generation booster candidate generated a higher immune response (as measured by neutralizing antibody titers) than Pfizer-BioNTech’s booster or the Sanofi-GSK first-generation booster, both of which target the original D614 parent strain. The proportion of participants with at least a 10-fold increase in neutralizing antibody titers for the original D614 SARS-CoV-2 strain between day 0 and day 15 was: • 76.1% (95% CI 64.5–85.4) for the Sanofi-GSK next-generation booster, vs • 63.2% (95% CI 51.3–73.9) for the Pfizer BioNTech D614 booster, and • 55.3% (95% CI 43.4–66.7) for the Sanofi-GSK D614 (firstgeneration parent booster candidate). In this study, which included 247 subjects, all the three vaccines also elicited neutralizing antibodies against the Omicron BA.1 variant, with highest responses generated by the Sanofi-GSK next-generation candidate. Results of COVIBOOST study are available on a pre-print server, pending publication in a peer-reviewed journal. Across both studies, the SanofiGSK next-generation vaccine candidate was well-tolerated, with a favorable safety profile. In the VAT02 cohort 2 study, low numbers (less than 4%) of Grade 3 reactions were reported, all transient and non-severe.

SMARMORE CASTLE CLINIC GAINS MAJOR INTERNATIONAL ACCREDITATION

Smarmore Castle Clinic, a 32-bed detox and addiction rehab clinic near Ardee, Co. Louth, has been awarded a major international accreditation recognising Excellence in International Best Practice, Legislation and Regulatory Standards. The prestigious award was received from the Comparative Health Knowledge System (CHKS), a UK health organisation which provides independent recognition of commitment to quality improvement for boards, external regulators and patients. The CHKS award follows a comprehensive assessment by a team of external senior healthcare professionals which examined a range of activities undertaken at Smarmore Castle Clinic.

Located in a 13th century castle, and surrounded by 15 acres of gardens, Smarmore Castle Clinic offers an unrivalled environment in which patients can take the first steps on the road to recovery from addiction.

News of the recognition comes as the Health Service Executive (HSE) has entered into an agreement with Smarmore Castle Clinic to provide public funding for patients in need of inpatient detox and rehab from alcohol and drugs. Moyra Amess, Director, Assurance & Accreditation at CHKS stated, “The accreditation process requires dedication and commitment. Every organisation we make this award to has proved to our external assessors that its standards and process meet international best practice standards. This is a significant achievement.” For Keith Cassidy, Clinic Manager at Smarmore Castle Clinic, the recognition reflects its high standards of care and successful outcomes for patients. “We are delighted to receive this esteemed award which recognises the tireless work undertaken in this clinic towards the rehabilitation of patients. Our healing and selfreflective approach seek to show both patients and their families that there is life after addiction. Lives can be rebuilt.

“Smarmore Castle Clinic has quickly become one of the leading addiction treatment centres in Ireland and we are committed to offering people freedom from addiction. We will continue to improve our services in the months and years ahead, with recovery front and centre of everything that we do.

“Considering six out of ten people have direct experience of addiction, we are also now particularly pleased to have the opportunity to work with the HSE and other agencies in addressing the challenge of addiction.” Smarmore Castle Clinic’s medical team is led by two of Ireland’s leading addiction specialists, medical director Dr Hugh Gallagher and consultant psychiatrist, Professor Gerry Lynch. The clinic provides a distinctive therapeutic and medical programme for those suffering from alcoholism, drug and behavioural addictions. The treatment plan offered is based on the successful Minnesota Model 12-step treatment programme. The clinic also offers a much sought-after dual diagnosis programme that directly treats patients who have both addiction and mental health issues. Indeed, Smarmore’s on-site 24-hour medical team enables the clinic to offer a full medically managed detox where necessary.

Dr Hugh Gallagher, Medical Director and Keith Cassidy, Clinic Manager

Whether your patients’ moderate-to-severe AD is FIERCE or TAMER,

CIBINQO is a convenient once-daily oral JAK1 inhibitor for moderate-to-severe atopic dermatitis (AD) that o ers1-4

Signifi cant skin clearance

at week 12, with sustained control at week 481,5

Rapid itch relief, superior to

dupilumab + TCS at week 2 for CIBINQO 200 mg + TCS, with

signifi cant results as early as day 41,6 A once-daily pill available in multiple doses that can be used with or without medicated topical therapies so you can tailor treatment to meet the individual needs of your patients1-3,7,8

CONSISTENT SAFETY PROFILE: Rigorously studied in >3100 patients across 7 clinical trials, including one ongoing LTE9

PRESCRIBING INFORMATION CIBINQO® ▼ (ABROCITINIB)

Please refer to full Summary of Product Characteristics (SmPC) before prescribing Cibinqo®. Presentation: Film-coated tablets containing 50 mg, 100 mg, or 200 mg abrocitinib. Each tablet contains 1.37 mg, 2.73 mg, and 5.46 mg of lactose monohydrate, respectively. Indications: For the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Dosage: Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of atopic dermatitis. Posology: The recommended starting dose is 200 mg once daily. A starting dose of 100 mg once daily is recommended for patients ≥ 65 years of age. For other patients who may benefi t from a starting dose of 100 mg, see sections 4.4 and 4.8 of the SmPC. During treatment, the dose may be decreased or increased based on tolerability and e cacy. The lowest e ective dose for maintenance should be considered. The maximum daily dose is 200 mg. Can be used with or without medicated topical therapies for atopic dermatitis. Discontinuation of treatment should be considered in patients who show no evidence of therapeutic benefi t after 24 weeks. Treatment initiation: Treatment should not be initiated in patients with a platelet count < 150 × 103/mm3, an absolute lymphocyte count (ALC) < 0.5 × 103/mm3, an absolute neutrophil count (ANC) < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Dose interruption: If a patient develops a serious infection, sepsis or opportunistic infection, dose interruption should be considered until the infection is controlled. Interruption of dosing may be needed for management of laboratory abnormalities. Missed doses: If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, dosing should be resumed at the regular scheduled time. Interactions: In patients receiving dual strong inhibitors of cytochrome CYP2C19 and moderate inhibitors of CYP2C9, or strong inhibitors of CYP2C19 alone (e.g., fl uvoxamine, fl uconazole, fl uoxetine and ticlopidine), the recommended starting dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. Treatment is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g., rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin). Renal impairment: No dose adjustment is required in patients with mild renal impairment, i.e., estimated glomerular fi ltration rate (eGFR) of 60 to < 90 mL/min. In patients with moderate (eGFR 30 to < 60 mL/min) renal impairment, the recommended dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. In patients with severe (eGFR < 30 mL/min) renal impairment, 50 mg once daily is the recommended starting dose. The maximum daily dose is 100 mg. Cibinqo has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy. Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Cibinqo must not be used in patients with severe (Child Pugh C) hepatic impairment. Elderly: The recommended starting dose for patients aged 65 years or more 100 mg once daily. Paediatric population: The safety and e cacy of Cibinqo in children under 12 years of age have not yet been established. No data are available. Cibinqo has been studied in adolescents 12 to < 18 years of age. However, because of bone fi ndings in juvenile rats (comparable to a 3 month old human), additional long-term data in growing adolescents is needed to conclude that the benefi ts outweigh the risks. Method of administration: This medicinal product is to be taken orally once daily with or without food at approximately the same time each day. In patients who experience nausea, taking Cibinqo with food may improve nausea. Tablets should be swallowed whole with water and should not be split, crushed, or chewed because these methods have not been studied in clinical trials. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Active serious systemic infections, including tuberculosis (TB), severe hepatic impairment, pregnancy, and breast-feeding. Warnings and Precautions: Serious infections: Serious infections have been reported in patients receiving Cibinqo. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster and pneumonia. Treatment must not be initiated in patients with an active, serious systemic infection. Risks and benefi ts of treatment prior to initiating Cibinqo should be considered. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with abrocitinib. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. The patient should be closely monitored, and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Tuberculosis: Patients should be screened for TB before starting treatment and yearly screening for patients in highly endemic areas for TB should be considered. Abrocitinib must not be given to patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of treatment. Viral reactivation: Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies. The rate of herpes zoster infections was higher in patients 65 years of age and older and patients with severe atopic dermatitis at baseline. If a patient develops herpes zoster, temporary interruption of treatment should be considered until the episode resolves. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy and during therapy. Patients with evidence of active hepatitis B or hepatitis C (positive hepatitis C PCR) infection were excluded from clinical studies. Patients who were hepatitis B surface antigen negative, hepatitis B core antibody positive, and hepatitis B surface antibody positive had testing for hepatitis B virus (HBV) DNA. Patients who had HBV DNA above the lower limit of quantifi cation (LLQ) were excluded. Patients who had HBV DNA negative or below LLQ could initiate treatment; such patients had HBV DNA monitored. If HBV DNA is detected, a liver specialist should be consulted. Vaccination: No data are available on the response to vaccination in patients receiving Cibinqo. Use of live, attenuated vaccines should be avoided during or immediately prior to treatment. Prior to initiating treatment with this medicinal product, it is recommended that patients be brought up to date with all immunisations, including prophylactic herpes zoster vaccinations, in agreement with current immunisation guidelines. Thrombotic events including pulmonary embolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving abrocitinib. Cibinqo should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, prothrombotic disorder, use of combined hormonal contraceptives or hormone replacement therapy, patients undergoing major surgery or prolonged immobilisation. If clinical features of DVT/PE occur, treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Malignancy (including non-melanoma skin cancers): Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical studies with abrocitinib. Clinical data are insu cient to assess the potential relationship of exposure to abrocitinib and the development of malignancies. Long-term safety evaluations are ongoing. The risks and benefi ts of Cibinqo treatment should be considered prior to initiating in patients with a known malignancy other than a successfully treated NMSC or cervical cancer in situ or when considering continuing Cibinqo therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Haematologic abnormalities: Confi rmed ALC < 0.5 × 103/mm3 and platelet count < 50 × 103/mm3 were observed in less than 0.5% of patients in clinical studies. Treatment with abrocitinib should not be initiated in patients with a platelet count < 150 × 103/mm3, an ALC < 0.5 × 103/mm3, an ANC < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Complete blood count should be monitored 4 weeks after initiation of therapy and thereafter according to routine patient management. Lipids: Dose dependent increases in blood lipid parameters were reported in patients treated with abrocitinib compared to placebo. Lipid parameters should be assessed approximately 4 weeks following initiation of therapy and thereafter according to the patient’s risk for cardiovascular disease. The e ect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Patients with abnormal lipid parameters should be further monitored and managed according to clinical guidelines, due to the known cardiovascular risks associated with hyperlipidaemia. In patients with a high burden of cardiovascular risk factors, the risks, and benefi ts of abrocitinib compared to that of other available therapies for atopic dermatitis should be considered. If abrocitinib is chosen, interventions to manage lipid concentrations should be implemented according to clinical guidelines. Elderly: The safety profi le observed in elderly patients was similar to that of the adult population with the following exceptions: a higher proportion of patients 65 years of age and older discontinued from clinical studies and were more likely to have serious adverse reactions compared to younger patients; patients 65 years and older were more likely to develop low platelet and ALC values; the incidence rate of herpes zoster in patients 65 years of age and older was higher than that of younger patients. There are limited data in patients above 75 years of age. Immunosuppressive conditions or medicinal products: Patients with immunodefi ciency disorders or a fi rst-degree relative with a hereditary immunodefi ciency were excluded from clinical studies and no information on these patients is available. Combination with biologic immunomodulators, potent immunosuppressants such as ciclosporin or other Janus kinase (JAK) inhibitors has not been studied. Their concomitant use with abrocitinib is not recommended as a risk of additive immunosuppression cannot be excluded. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase defi ciency or glucose-galactose malabsorption should not take this medicinal product. Drug Interactions:Potential for other medicines to a ect pharmacokinetics of abrocitinib: Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be a ected by medicinal products that strongly inhibit or induce theses enzymes and transporter. Dose adjustments, as appropriate, may be required. Co-administration with products which increase gastric pH: The e ect of elevating gastric pH with antacids, H2-receptor antagonists (famotidine), or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may reduce the absorption of abrocitinib due to the low solubility of abrocitinib at pH above 4. Potential for Cibinqo to a ect pharmacokinetics of other medicinal products: No clinically signifi cant e ects of Cibinqo were observed in drug interaction studies with oral contraceptives. Caution should be exercised for concomitant use of abrocitinib with dabigatran. Caution should be exercised as the levels of P-gp substrates with a narrow therapeutic index, such as digoxin, may increase. The exposures of medicinal products metabolised by CYP2B6 (e.g., bupropion, efavirenz) and CYP1A2 (e.g., alosetron, duloxetine, ramelteon, tizanidine) may be decreased and of those metabolised by CYP2C19 (e.g., S mephenytoin) may be increased initially and then decreased, when used concomitantly with abrocitinib. Fertility, pregnancy, and lactation: Women of childbearing potential: Women of reproductive potential should be advised to use e ective contraception during treatment and for 1 month following the fi nal dose of Cibinqo. Pregnancy planning and prevention for females of reproductive potential should be encouraged. Pregnancy: There are no or limited amount of data on the use of abrocitinib in pregnant women. Studies in animals have shown reproductive toxicity. Abrocitinib has been shown to cause embryo-foetal lethality in pregnant rats and rabbits, skeletal variations in the foetuses of pregnant rats and rabbits and to a ect parturition and peri/postnatal development in rats. Cibinqo is contraindicated during pregnancy. Breast-feeding: There are no data on the presence of abrocitinib in human milk, the e ects on the breast fed infant, or the e ects on milk production. Abrocitinib was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and Cibinqo is contraindicated during breast feeding. Fertility: Based on the fi ndings in rats, oral administration of Cibinqo may result in temporary reduced fertility in females of reproductive potential. The e ects on female rat fertility were reversible 1 month after cessation of abrocitinib oral administration. Driving and operating machinery: Cibinqo has no e ect on the ability to drive or use machines. Side E ects: The most commonly reported adverse reactions are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), vomiting (3.5%), dizziness (3.4%) and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) including herpes simplex, herpes zoster, and pneumonia. Refer to SmPC for further information on side e ects. Legal Category: S1A. Marketing Authorisation Numbers: EU/1/21/1593/002 - Cibinqo 50 mg (28 fi lm-coated tablets), EU/1/21/1593/007 - Cibinqo 100 mg (28 fi lm-coated tablets); EU/1/21/1593/012 - Cibinqo 200 mg (28 fi lm-coated tablets). Marketing Authorisation Holder: Pfi zer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact Pfi zer Medical Information on 1800 633 363 or at medical.information@pfi zer.com. For queries regarding product availability please contact: Pfi zer Healthcare Ireland, Pfi zer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467 6500. ▼ This medicinal product is subject to additional monitoring. This will allow quick identifi cation of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. Last revised: December 2021. Ref: CQ 1_0 IE.

References: 1. Bieber T, Simpson EL, Silverberg JI, et al. N Engl J Med. 2021;384(12):1101-1112. 2. Simpson EL, Sinclair R, Forman S, et al. Lancet. 2020;396(10246):255-266. 3. Silverberg JI, Simpson EL, Thyssen JP, et al. JAMA Dermatol. 2020;156(8):863-873. 4. Boeri M, Sutphin J, Hauber B, et al. J Dermatolog Treat. 2020 Nov 2:1-10. doi:10.1080/09546634.1832185. 5. Reich K, Silverberg JI, Papp K, et al. Presented at the Revolutionizing Atopic Dermatitis Virtual Conference; 13 June 2021. 6. Ständer S, Yosipovitch G, Simpson EL, et al. Presented at the American Academy of Dermatology Virtual Meeting Experience 2021; 23-25 April 2021. 7. Cibinqo Summary of Product Characteristics. 8. Blauvelt A, Silverberg JI, Lynde CW, et al. J Am Acad Dermatol. Published online 17 August 2021. doi: 10.1016/j.jaad.2021.05.075. 9. Cork MJ, Deleuran MS, Geng B, et al. Presented at the European Academy of Dermatology and Venereology Virtual Congress 2021; 29 September-2 October 2021. Although some clinical trials included adolescents, please note that CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. TCS includes low- to medium-potency topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors, per protocol guidance in JADE COMPARE. Nonmedicated topicals were also required.1 AD=atopic dermatitis; JAK=Janus kinase; LTE=long-term extension.