Summary of the risk management plan (RMP) for Plegridy (peginterferon beta-1a)

Transcription

1 EMA/329000/2014 Rev.1 Summary of the risk management plan (RMP) for Plegridy (peginterferon beta-1a) This is a summary of the risk management plan (RMP) for Plegridy, which details the measures to be taken in order to ensure that Plegridy is used as safely as possible. For more information on RMP summaries, see here. This RMP summary should be read in conjunction with the EPAR summary and the product information for Plegridy, which can be found on Plegridy s EPAR page. Overview of disease epidemiology Plegridy is used to treat the relapsing-remitting form of multiple sclerosis (MS). MS is a disease in which the body s immune system malfunctions and attacks parts of the central nervous system (the brain and spinal cord). This causes inflammation and destroys the protective sheath around the nerves, leading to progressive disability. Onset of MS is usually between the ages of 20 and 40 years, and rarely occurs in children or in adults 60 years and older. Approximately twice as many women than men have MS. About 85% of people with MS initially have the relapsing-remitting form, characterised by occasional flare-ups of the disease, called relapses, in between periods when the disease is inactive. About half of patients with MS relapses go on to develop progressive MS within 10 to 20 years after diagnosis. The total number of people with MS worldwide is estimated to be between 2 to 2.5 million, and approximately 93 of every 100,000 persons in Europe have MS. Summary of treatment benefits Plegridy is a medicine that contains the active substance peginterferon beta-1a. It is available as a solution for injection under the skin. The peginterferon beta-1a in Plegridy is a pegylated interferon (a protein naturally produced by the body), which is removed from the body at a slower rate than other interferons, allowing the medicine to be given less often. Plegridy was investigated in 1,516 patients in one main study, in which it was compared with placebo (a dummy treatment). Plegridy showed about a 30% reduction in the number of relapses in patients with relapsing-remitting MS compared with placebo, which is comparable to the effect of other MS medicines containing interferon beta, and is considered clinically relevant. When given every two weeks, Plegridy was also shown to slow down disease progression. Unknowns relating to treatment benefits Peginterferon beta-1a has not been studied in patients under the age of 18 years or over the age of 65 years, in pregnant and/or breastfeeding women, or in patients with hepatic impairment (liver function problems). Furthermore, no direct comparison with non-pegylated interferons has been done, which should be considered when switching patients between pegylated and non-pegylated interferons. Peginterferon beta-1a will not cure MS, but rather improve its symptoms and it is not effective in patients with the progressive forms of MS. Page 1/6

2 Summary of safety concerns Important identified risks Risk Preventability Serious hypersensitivity (allergic) reactions Hepatic (liver) injury Low blood-cell counts Serious injection site reactions including injection site necrosis (sores) Flu-like symptoms Serious allergic reactions may occur uncommonly during treatment with Plegridy (seen in less than 1 in 100 people). Signs and symptoms that may be experienced during a serious allergic reaction include: - difficulty breathing; - swelling around the face (lips, tongue, or throat); - skin rashes or redness. Liver problems may be seen in less than 1 in 10 people during treatment with Plegridy. During treatment with Plegridy, patients may develop low numbers of white blood cells (seen in less than 1 in 10 people) or platelets (seen in less than 1 in 100 people), which can cause an increased risk of infection, or bleeding. Patients may get serious irritation at the injection site (seen in less than 1 in 1,000 people), which can lead to skin and tissue damage (injection site necrosis). During treatment with Plegridy, flu-like symptoms may affect more than 1 in 10 people. These symptoms include: - headache; - muscle pain (myalgia); - pain in joints, arms, legs or neck Patients should not use peginterferon beta-1a if they are allergic to peginterferon beta-1a, interferon beta- 1a, or any of the other ingredients of Plegridy. Patients should contact a doctor immediately if they experience symptoms of an allergic reaction. Peginterferon beta-1a should be discontinued if serious hypersensitivity reactions occur. Patients should call a doctor immediately if they get yellowing of the skin or eyes (jaundice), itch all over the body, bruise easily or feel sick or vomit. These may be signs of a possible liver problem. Doctors may do blood tests from time to time to make sure that the patients liver and blood values are within the normal range. The doctor may do blood tests from time to time to make sure that a patient s blood count is within the normal range. Patients should speak with their doctor, pharmacist or nurse before injecting peginterferon beta-1a if they experience infections or bleeding. They may get worse while using peginterferon beta-1a. When patients are ready to inject the medicine, they should carefully follow the instructions in section 7 of the package leaflet, Instructions for injecting Plegridy which explain how to reduce the risk of injection site reactions. If patients experience any break in the skin together with swelling or fluid leaking around the injection site, they should contact their doctor for advice. The impact of flu-like symptoms may be reduced by: - injecting peginterferon beta-1a just before bedtime. This may allow patients to sleep through the effects. - taking paracetamol or ibuprofen half an Page 2/6

3 Risk Preventability Depression, suicidal behaviour Seizures (fits or convulsions) Thyroid disorders (arthralgia); - chills, feeling cold; - fever; - feeling weak and tired (asthenia). Flu-like symptoms are more common when patients first start using peginterferon beta-1a. They gradually get less frequent as a patient keeps using peginterferon beta-1a. Depression has been seen in less than 1 in 10 people during treatment with Plegridy. MS increases the chance that a patient can develop fits or seizures. Seizures were seen in less than 1 in 100 people taking Plegridy. Patients with MS have an increased chance of developing thyroid disorders, particularly an underactive thyroid. This risk may be even higher in patients taking peginterferon beta-1a. hour before a peginterferon beta-1a injection and continuing to take it for up to a day. Patients should speak with their doctor or pharmacist about a suitable dose. - drinking plenty of water to stay hydrated if they develop a fever. If patients experience any of the following: - feeling unusually sad, anxious, or worthless, - have thoughts about suicide, they should contact their doctor immediately. Patients with depression should be monitored closely during therapy and treated appropriately. Stopping therapy with Plegridy should be considered. Plegridy should be administered with caution to patients with a history of seizures and to those receiving treatment with antiepileptic medicines, particularly if their epilepsy is not adequately controlled with medication. If patients have epilepsy or other seizure disorders, not controlled by medication, they should talk to their doctor, pharmacist, or nurse before injecting peginterferon beta-1a. If a patient experiences a seizure or a fit, they should contact a doctor immediately. The doctor may do blood tests from time to time to make sure that a patient s thyroid function is normal. Patients with thyroid problems should talk to their doctor, pharmacist, or nurse before injecting peginterferon beta-1a. Important potential risks Risk Cardiac (heart) disorders Worsening of cardiac disease has been reported in patients receiving interferon beta. If patients develop heart problems, which can cause symptoms such as chest pain (angina), particularly after any activity; swollen Page 3/6

4 Risk Cancer Immunogenicity (ability of a substance to provoke an immune response) Systemic lupus erythematosus (SLE) Thrombotic microangiopathies (TMAs) including thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) Nephrotic syndrome / glomerulosclerosis (kidney disorders) ankles; shortness of breath (congestive heart failure); or an irregular heartbeat (arrhythmia), they should talk to their doctor, pharmacist, or nurse before injecting peginterferon beta-1a. Beta interferons affect the immune system and this might be associated with the development of cancer. No increased risk of cancer was observed in the studies using peginterferon beta-1a. Antibodies against peginterferon beta-1a were seen in less than 1% of patients treated with Plegridy. These antibodies had no effect on the safety or efficacy of peginterferon beta-1a. Patients with SLE, a disease where the immune system attacks the body s own tissue, have raised levels of interferons (including interferon beta-1a) in the blood, and these are linked to disease activity, suggesting they may play a role in causing the disease. However, there were no reported cases of SLE from the Plegridy placebo-controlled studies in the patients with MS. Cases (including fatal cases) of TMA, a rare and serious condition associated with the formation of blood clots in the small blood vessels, have been reported with interferon beta products indicated for the treatment of MS. There were no reported cases of TMA from the main studies with Plegridy in patients with MS. Cases of various kidney disorders resulting in nephrotic syndrome (abnormal function of the kidney leading to loss of protein in the urine and fluid build-up in the body) have been reported during treatment with interferon beta products. There were no reported cases of nephrotic syndrome or glomerulosclerosis from the Plegridy placebo-controlled studies in the patients with MS. Missing information Risk Use in paediatric patients Use in older patients Effects on pregnancy and use in breastfeeding women Use in patients with hepatic impairment (reduced liver function) Plegridy has not been studied in patients under 18 years of age. Plegridy has not been studied in patients over 65 years of age. Treatment with Plegridy should not be started in pregnant patients. Patients who could get pregnant should use contraception during treatment with Plegridy. Patients planning to have a baby, or who become pregnant while using Plegridy, should tell their doctor to discuss possible treatment discontinuation. Patients wishing to breastfeed while using Plegridy should speak with their doctor first. Plegridy has not been studied in patients with reduced liver function, as these patients were excluded from participating in clinical trials. Caution should be used and close monitoring should be considered when administering peginterferon beta-1a to patients with severe liver function problems. Patients Page 4/6

5 Risk Safety in patients with decreased peripheral blood counts Drug-drug interaction should be monitored for signs of reduced liver function and caution should be exercised when interferons are used alongside other medicines associated with liver injury. Plegridy has not been studied in patients with a history of abnormal peripheral blood cell counts, as these patients were excluded from clinical trials. During treatment with Plegridy, patients may develop a low number of white blood cells or platelets, which can cause an increased risk of infection or bleeding. Patients should speak with their doctor, pharmacist or nurse before injecting peginterferon beta-1a if they experience infections or bleeding. They may get worse while using peginterferon beta-1a. The doctor may do blood tests from time to time to make sure that the patient s blood cell counts are within the normal range. No formal studies have been conducted on possible interactions between Plegridy and other medicines. Summary of risk minimisation measures by safety concern All medicines have a summary of product characteristics (SmPC) which provides physicians, pharmacists and other healthcare professionals with details on how to use the medicine, and also describes the risks and recommendations for minimising them. Information for patients is available in lay language in the package leaflet. The measures listed in these documents are known as routine risk minimisation measures. The SmPC and the package leaflet are part of the medicine s product information. The product information for Plegridy can be found on Plegridy s EPAR page. This medicine has no additional risk minimisation measures. Planned post-authorisation development plan List of studies in post-authorisation development plan Study/activity (including study number) Paediatric study Objectives How safe, well Safety concerns /efficacy issue addressed Growth (height, Status Planned date for submission of (interim and) final results Planned 2021 tolerated, and weight); effective psychiatric peginterferon monitoring, beta-1a is in including adolescents and depression; vital children between signs, cardiac 10 and 18 years testing, changes of age. in laboratory values; MS relapse rate at 2 years. Page 5/6

6 European Interferon Beta Pregnancy Registry To evaluate pregnancy outcomes, including frequency of spontaneous abortion, and frequency of birth defects. To address findings from experimental studies of spontaneous abortions in monkeys receiving high doses of nonpegylated1 interferon beta-1a. Started with premarketing clinical trials and will continue post-marketing. PSURs sent to regulators. In Europe, an annual report is submitted with combined data from all marketing authorisation holders enrolled in the registry. Phase 3 Extension Study, 105MS302 To assess how effective, safe, and well tolerated peginterferon beta-1a is in subjects originally treated in Study 105MS301 who continue peginterferon beta-1a treatment. Clinical safety tests, tests for depression, changes in laboratory values, and immunogenicity. Ongoing Final report by March 2016 Studies which are a condition of the marketing authorisation None. Summary of changes to the risk management plan over time Not applicable. This summary was last updated in This document has been updated; the previous version referred to peginterferon beta-1a. Page 6/6