26 minute read
Feature: Bladder Cancer
Positive Outcomes in Bladder Cancer
Risk factors, warning signs and the positive outcomes of early detection
Each year in Ireland, 491 men and women are diagnosed with bladder cancer. Sadly, around 222 people die from the disease each year. But this does not have to be the case. When detected early, bladder cancer is very treatable. Bladder cancer begins when cells in the bladder start to grow uncontrollably. As more cancer cells develop, they can form a tumour which can spread to other areas of the body. It usually takes a long time to develop, so it is most common in older people. 3 in 4 people (over 75%) who get bladder cancer in Ireland are 65 years or older. Although less common in people under 50, it is very worthwhile staying vigilant. More men than women get bladder cancer. This may be because more men than women have smoked or been exposed to chemicals/dyes at work in recent decades.
We don’t know exactly what causes most bladder cancers but there are some factors that may increase your risk Smoking cigarettes increases your risk of bladder cancer. Over a third of all bladder cancers are caused by smoking. Your risk of getting bladder cancer if you smoke is up to 4 times that of someone who has never smoked.
People with the highest risk are those who:
• smoke heavily • started smoking at an early age • have smoked for a long time • Cigar and pipe smoking can also increase your risk. Certain industrial chemicals have been linked with bladder cancer. Workers in other industries that use certain organic chemicals also may have a higher risk of bladder cancer. It is always worth checking with your Health and Safety officer, about your safety when using certain chemicals. Thankfully there is far more regulation around the use and exposure to chemicals than there was many years ago. If you have been diagnosed with bladder cancer, it is worth finding out if you have ever been exposed to a chemical mentioned here. If you have, talk to your urologist or cancer doctor.
• Arylamines • Polycyclic aromatic hydrocarbons • Chlorine and trihalomethanes
• Chlorine
There are also risk factors that are beyond your control Race and ethnicity – Caucasians are about twice as likely to develop bladder cancer as Black and Hispanic people. Asian Americans and Native Americans have slightly lower rates of bladder cancer. The reasons for these differences are not well understood.
Age – Bladder cancer usually takes a long time to develop, so it is most common in older people. 3 in 4 people (over 75%) who get bladder cancer in Ireland are 65 years or older. It is rarer in people under 50. Gender – Bladder cancer is much more common in men than in women.
Chronic bladder irritation
and infections – Urinary tract infections, kidney and bladder stones, bladder catheters left in place a long time, and other causes of chronic bladder irritation have been linked with bladder cancer (especially squamous cell carcinoma of the bladder), but it’s not clear if they cause bladder cancer.
Written by Helen Forristal, MSc (ANP) BSc (Professional Nursing) ENB 237 (Oncology Nursing), Director of Nursing Services at The Marie Keating Foundation
Personal history of bladder or other urothelial cancers such as kidney
Genetics and family history –
People who have family members with bladder cancer have a higher risk of getting it themselves.
Prior chemotherapy or radiation therapy
Signs and symptoms
These are the possible symptoms of bladder cancer. Your symptoms are unlikely to be cancer, but it’s important to get them checked by a doctor.
Blood in the urine
Blood in the urine is the most common symptom of bladder cancer. 4 out of 5 people with bladder cancer (80%) have some blood in their urine. Doctors call blood in the urine haematuria (pronounced heem-at-you-ree-ah). It is important to remember that blood in urine can sometimes be caused by stones in the urinary tract, a Urinary Tract Infection or even Prostatitis. Sometimes the blood is there in such small amounts that you can’t see it.(called microscopic haematuria) But a urine test will still show if blood is present and if it is further tests will be carried out. The bleeding is not usually painful but tell your doctor whether you had any pain when you peed (passed urine) with blood in it as it will help them to make their diagnosis. It can also help your doctor if you tell them whether: • There is blood only when you start to pee • The blood is mixed with all the urine you pass Problems with passing urine may be a symptom of other conditions but a bladder cancer should be ruled out. You should see your doctor if you: • Notice blood in your urine • Need to pass urine very often • Need to pass urine very suddenly • Have pain when passing urine Please go to your doctor if you have any concerns, it is better to have these signs and/or symptoms checked out early and remember that early detection saves lives. Many cancers can be treated and potentially cured if caught early.
For more information and support around bladder cancer or any of the most common cancers please go to www. mariekeating.ie or reach out to info@mariekeating.ie with any questions.
• After at least 5 years of follow up KEYTRUDA monotherapy continued to show improved OS, ORR, and DOR compared with investigators choice of chemotherapy for patients with advanced platinum-resistant or platinum-refractory urothelial carcinoma.2
Results from KEYNOTE-045: A multicentre, open-label, randomised, phase 3 trial comparing KEYTRUDA with investigators choice of chemotherapy for patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy.1,2
5 Year Results1-3
Superior Overall Survival 29% reduction in risk of death (HR, 0.71 [95%CI, 0.59–0.86] Median OS: KEYTRUDA 10.1 months vs Chemotherapy 7.2 months Longer Duration of Response KEYTRUDA 29.7 months vs Chemotherapy 4.4 months Objective Response Rate KEYTRUDA 21.9% vs Chemotherapy 11.0% There was no statistically significant difference between KEYTRUDA and Chemotherapy with respect to Progression Free Survival. Median PFS: KEYTRUDA 2.1 months vs Chemotherapy 3.3 months (HR, 0.95 [95%CI, 0.79-1.14]
After 5 years of follow up safety was consistent with that of previous reports.2 In the as-treated population, any grade treatment related adverse events of any cause occurred in 62% of participants in the pembrolizumab group and 90.6% of participants in the chemotherapy group. Grade 3 or worse adverse events of any cause occurred in 16.9% in the pembrolizumab group and 50.2% in the chemotherapy group.3
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. 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 Alert 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 hepatic impairment. No studies in moderate or 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-related adverse reactions Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. Most immune related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Immune related adverse reactions have also occurred after the last dose of pembrolizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. Immune-related adverse reactions are immune-related pneumonitis, immune-related colitis, immune-related hepatitis, immune-related nephritis, immune-related endocrinopathies (including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism), Immune-related skin adverse reactions (also including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)), Refer to SmPC for more information and management of immune-related 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. 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-related adverse reactions. Most of these reactions resolved with appropriate medical treatment or withdrawal of pembrolizumab. The most serious adverse reactions were immune-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, insomnia, 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, dysgeusia, dyspnoea, cough, nausea, diarrhoea, vomiting, abdominal pain, constipation, alopecia, rash, pruritus, arthralgia, musculoskeletal pain, myositis, pyrexia, fatigue, asthenia, oedema, ALT increase, AST increased. Common: pneumonia, febrile neutropenia, lymphopenia, infusion related reaction, adrenal insufficiency, thyroiditis, hyperthyroidism, hyponatraemia, hypocalcaemia, lethargy, dry eye, cardiac arrhythmia (including atrial fibrillation), hypertension, pneumonitis, colitis, gastritis, dry mouth, hepatitis, severe skin reactions, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, pain in extremity, arthritis, acute kidney injury, influenza-like illness, chills, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased. 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: June 2022. © 2022 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. II111
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 (pembrolizumab) SmPC. Available at: www.medicines.ie. Accessed July 2022 2. Bellmunt J et al. Five-year follow-up from phase III KEYNOTE-045 trial: Pembrolizumab versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer. Poster (4532) presented ASCO 2021; virtual. 3. Necchi A et al. Three-year follow up from phase III KEYNOTE-045 trial: Pembrolizumab versus investigator’s choice (paclitaxel, docetaxel, or vinflunine) in recurrent, advanced urothelial cancer. Poster (919P) presented at ESMO 2019.
24
Epilepsy A Focus on SUDEP
Written by Paddy McGeoghegan - Epilepsy Ireland Advocacy & Communications Manager
SUDEP is a word which can strike fear and worry amongst people with epilepsy and their families. In advance of SUDEP Action Day 2022 on October 19th, I was pleased to write about this often undiscussed, rare but devastating aspect of epilepsy. Epilepsy-related deaths can be due to several factors – because of a prolonged seizure (status epilepticus) or seizure-related injury or drowning. Another major cause of epilepsyrelated deaths is SUDEP. Overall, it is estimated that there are approximately 130 epilepsyrelated deaths in Ireland each year. Of these, it estimated that 21-40 are due to SUDEP. An Epilepsy Ireland funded study being conducted by Dr. Yvonne Langan of St. James’s Hospital Dublin is currently seeking to establish a clearer picture of SUDEP and epilepsy-related death incidence in Ireland.
SUDEP stands for Sudden Unexpected Death in Epilepsy and is defined where there is death in a patient with epilepsy that is not due to trauma, drowning, status epilepticus, or other known causes but for which there is often evidence of an associated seizure.
Unfortunately, there is still a lot we don’t about SUDEP. Globally, epilepsy researchers are working to find out what the exact causes of SUDEP are. It is believed that respiratory abnormalities and/or cardiac arrhythmias play a central role. However, the exact mechanism behind why and how this happens remains unclear.
In the past, SUDEP was a subject that many people with epilepsy, their family members and their clinicians did not want to discuss. However, attitudes have changed. In 2020, an Epilepsy Ireland survey of 323 people with epilepsy revealed that 81% of people with epilepsy wanted to know more about SUDEP. At Epilepsy Ireland, we are hopeful that research will eventually provide the answers to the questions about SUDEP we have today. However, in the absence of this breakthrough, it is best to focus on what we DO know, rather than what we don’t.
We do know that the risk of SUDEP varies from low to very low. We do know that it can affect any age group of those living with epilepsy but is more common in younger adults. We do know that the better a person’s epilepsy is controlled, the lesser the risk of SUDEP. We do know that certain types of seizures are not associated with SUDEP, such as absence or myoclonic seizures. However, the risk is higher if you have generalised tonic-clonic seizures. We do know that there are risk factors for SUDEP – some of which can be reduced by a person better understanding their epilepsy and using techniques to self-manage the condition. Raising awareness of the risks to the epilepsy community and how they can be modified is the key aspect of SUDEP Action Day. There are actions that can be taken to help reduce the risk of SUDEP. Ensuring that people with epilepsy and their families are aware of these risks could help to avoid a potentially preventable death. On SUDEP Action Day, we also share stories from families who have sadly lost a loved one due to SUDEP. These harrowing stories lay bare the impact of this rare but devastating aspect of epilepsy. Unfortunately, a common thread amongst these stories is how the person themselves or the wider family were unaware of SUDEP.
As Hospital Professionals in varying areas of our health service, the opportunity to discuss SUDEP may present to you. Our message is to have the conversation. Our most recent survey found how people with epilepsy want to know about SUDEP whether perceived at being at high risk or not; they want to know about it sooner rather than later; and they want to hear about it from their trusted medical teams.
Knowledge is power for our community – and simply knowing about SUDEP could make a substantial difference to how that person approaches and manages their condition. I would invite readers of Hospital Professional News to join with us on October 19th to raise awareness of SUDEP; what can be done to reduce the risks; and remember those who are no longer with us. Please check out our website and all our social media channels in the lead up to the day and on the day itself. Our team are here to assist your patients with any information they may require on SUDEP so please do not hesitate to get in touch with us if we can assist you in any way.
Visit www.epilepsy.ie to learn more about SUDEP and SUDEP Action Day.
Some of the key findings of the 2020 Epilepsy Ireland survey on SUDEP
Strength of Balance
Indicated for the treatment of moderate to severe active rheumatoid arthritis in adults who have responded inadequately to, or are intolerant to one or more disease modifying anti-rheumatic drugs.1 May be used as monotherapy or in combination with methotrexate.1
Refer to Summary of Product Characteristics (SmPC) before prescribing, and for full prescribing information.
JYSELECA® filgotinib 100 mg or 200 mg film-coated tablets. Indication: Jyseleca is indicated for the treatment of moderate to severe active rheumatoid arthritis in adult patients who have responded inadequately to, or who are intolerant to one or more disease modifying anti rheumatic drugs (DMARDs). Jyseleca may be used as monotherapy or in combination with methotrexate (MTX). Dosage: Adults: 200 mg once daily. Taken orally with/without food. It is recommended that tablets are swallowed whole. Laboratory Monitoring: Refer to the SmPC for information regarding laboratory monitoring and dose initiation or interruption. Elderly: A starting dose of 100 mg once daily is recommended for patients aged 75 years and older as clinical experience is limited. Renal impairment: No dose adjustment required in patients with estimated creatinine clearance (CrCl) ≥ 60 mL/min. A dose of 100 mg of filgotinib once daily is recommended for patients with moderate or severe renal impairment (CrCl 15 to < 60 mL/min). Not recommended in patients with CrCl < 15 mL/min. Hepatic impairment: Mild/moderate hepatic impairment: no dose adjustment required. Severe hepatic impairment: not recommended. Children (< 18years): Safety and efficacy not yet established. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active tuberculosis (TB) or active serious infections. Pregnancy. Warnings/Precautions: See SmPC for full information. Immunosuppression: Combination use, with immunosuppressants e.g. ciclosporin, tacrolimus, biologics or other Janus kinase (JAK) inhibitors is not recommended as a risk of additive immunosuppression cannot be excluded. Infections: Infections, including serious infections such as pneumonia and opportunistic infections e.g. tuberculosis (TB), oesophageal candidiasis, and cryptococcosis have been reported. Risk benefit should be assessed prior to initiating in patients with risk factors for infections (see SmPC). Patients should be closely monitored for the development of signs and symptoms of infections during and after filgotinib treatment. Treatment should be interrupted if the patient is not responding to antimicrobial therapy, until infection is controlled. There is a higher incidence of serious infections in the elderly aged 75 years and older, caution should be used when treating this population. Tuberculosis: Patients should be screened for TB before initiating filgotinib, and filgotinib should not be administered to patients with active TB. Viral reactivation: Cases of herpes virus reactivation (e.g., herpes zoster), were reported in clinical studies (see SmPC). In rheumatoid arthritis clinical studies, the risk of herpes zoster appeared to be higher in female patients, Asian patients, patients ≥ 50 years of age, patients with a medical history of herpes zoster, patients with a medical history of chronic lung disease and patients treated with filgotinib 200 mg once daily. If a patient develops herpes zoster, filgotinib treatment should be temporarily interrupted until the episode resolves. Screening for viral hepatitis and monitoring for reactivation should be performed. Malignancy: Immunomodulatory medicinal products may increase the risk of malignancies. Malignancies were observed in clinical studies (see SmPC). Fertility: In animal studies, decreased fertility, impaired spermatogenesis, and histopathological effects on male reproductive organs were observed (see SmPC). The potential effect of filgotinib on sperm production and male fertility in humans is currently unknown. Haematological abnormalities: Do not start therapy, or temporarily stop, if Absolute Neutrophil Count (ANC) <1 × 109 cells/L, ALC <0.5 × 109 cells/L or haemoglobin <8 g/dL. Temporarily stop therapy if
JYSELECA – a JAK1 preferential inhibitor for moderate to severe RA1
JYSELECA shows more than 5x greater potency for JAK1 over JAK2/3 and TYK21* Balancing sustained efficacy2-6 with acceptable tolerability1,7
*This is based on biochemical assays, the clinical consequence of this is unknown. Common adverse events (≥1/100 to <1/10) include: nausea, upper respiratory tract infection, urinary tract infection, dizziness, lymphopenia.1
Visit strengthofbalance.co.uk to learn more
these values are observed during routine patient management. Vaccinations: Use of live vaccines during, or immediately prior to, filgotinib treatment is not recommended. It is recommended that immunisations, including prophylactic zoster vaccinations, be updated in agreement with current immunisation guidelines prior to initiating filgotinib treatment. Lipids: Treatment with filgotinib was associated with dose dependent increases in lipid parameters, including total cholesterol, and high-density lipoprotein (HDL) levels, while low density lipoprotein (LDL) levels were slightly increased (see SmPC). Cardiovascular risk: Rheumatoid arthritis patients have an increased risk for cardiovascular disorders. Patients should have risk factors (e.g., hypertension, hyperlipidaemia) managed as part of usual standard of care. Venous thromboembolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving JAK inhibitors including filgotinib. Caution should be used in patients with risk factors for DVT/PE, such as older age, obesity, a medical history of DVT/PE, or patients undergoing surgery, and prolonged immobilisation. Lactose content: Contains lactose; patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take filgotinib. Pregnancy/Lactation: Filgotinib is contraindicated in pregnancy. Filgotinib should not be used during breastfeeding. Women of childbearing potential must use effective contraception during and for at least 1 week after cessation of treatment. Driving/Using machinery: No or negligible influence, however dizziness has been reported. Side effects: See SmPC for full information. Common (≥1/100 to <1/10): nausea, upper respiratory tract infection, urinary tract infection, dizziness and lymphopenia Uncommon (≥1/1000 to <1/100): herpes zoster, pneumonia, neutropenia, hypercholesterolaemia and blood creatine phosphokinase increase. Serious side effects: See SmPC for full information Legal category: POM Pack: 30 filmcoated tablets/bottle Price: UK Basic NHS cost: £863.10; Ireland: POA Marketing authorisation number(s): Jyseleca 100mg film-coated tablets EU/1/20/1480/001 EU/1/20/1480/002 Jyseleca 200mg film-coated tablets EU/1/20/1480/003 EU/1/20/1480/004 Further information: Galapagos UK, Belmont House, 148 Belmont Road, Uxbridge UB8 1QS, United Kingdom 00800 7878 1345 medicalinfo@glpg.com Jyseleca® is a trademark. Date of Preparation: August 2022 IE-RA-FIL-202112-00003
Additional monitoring required
Adverse events should be reported. For Northern Ireland, reporting forms and information can be found at yellowcard.mhra.gov.uk or via the Yellow Card app (download from the Apple App Store or Google Play Store). Adverse events should also be reported to Galapagos via email to DrugSafety.UK.Ireland@glpg.com or 00800 7878 1345
Adverse events should be reported. For Ireland, reporting forms and information can be found at www.hpra.ie and can be reported to HPRA on +353 1 6764971. Adverse events should also be reported to Galapagos via email to DrugSafety.UK.Ireland@glpg.com or 00800 7878 1345
References: 1. JYSELECA SPC. Available at: www.medicines.org.uk / www.medicines.ie. Last accessed: September 2022. 2. Combe B, et al. Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219214. 3. Genovese MC, et al. JAMA 2019;322 (4):315–325. 4. Westhovens R, et al. Ann Rheum Dis 2021;doi:10.1136/annrheumdis-2020-219213. 5. Combe B, et al. Poster presented virtually at ACR, November 3–10, 2021. 6. Buch MH, et al. Poster presented virtually at ACR, November 3–10, 2021. 7. Genovese MC, et al. Poster presented virtually at the European League Against Rheumatism (EULAR) 2020 E-Congress, June 3–6, 2020.
