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.
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Summary of safety concerns Important identified risks Risk
What is known
Preventability
Serious
Serious allergic reactions may occur
Patients should not use peginterferon
hypersensitivity
uncommonly during treatment with
beta-1a if they are allergic to
(allergic)
Plegridy (seen in less than 1 in 100
peginterferon beta-1a, interferon beta-
reactions
people).
1a, or any of the other ingredients of
Signs and symptoms that may be
Plegridy. Patients should contact a doctor
experienced during a serious allergic
immediately if they experience
reaction include:
symptoms of an allergic reaction.
- difficulty breathing;
Peginterferon beta-1a should be
- swelling around the face (lips, tongue,
discontinued if serious hypersensitivity
or throat);
reactions occur.
- skin rashes or redness. Hepatic (liver)
Liver problems may be seen in less than
Patients should call a doctor immediately
injury
1 in 10 people during treatment with
if they get yellowing of the skin or eyes
Plegridy.
(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.
Low blood-cell
During treatment with Plegridy, patients
The doctor may do blood tests from time
counts
may develop low numbers of white blood
to time to make sure that a patient’s
cells (seen in less than 1 in 10 people) or
blood count is within the normal range.
platelets (seen in less than 1 in 100
Patients should speak with their doctor,
people), which can cause an increased
pharmacist or nurse before injecting
risk of infection, or bleeding.
peginterferon beta-1a if they experience infections or bleeding. They may get worse while using peginterferon beta-1a.
Serious
Patients may get serious irritation at the
When patients are ready to inject the
injection site
injection site (seen in less than 1 in
medicine, they should carefully follow
reactions
1,000 people), which can lead to skin
the instructions in section 7 of the
including
and tissue damage (injection site
package leaflet, “Instructions for
injection site
necrosis).
injecting Plegridy” which explain how to
necrosis (sores)
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.
Flu-like
During treatment with Plegridy, flu-like
The impact of flu-like symptoms may be
symptoms
symptoms may affect more than 1 in 10
reduced by:
people. These symptoms include:
- injecting peginterferon beta-1a just
- headache;
before bedtime. This may allow patients
- muscle pain (myalgia);
to sleep through the effects.
- pain in joints, arms, legs or neck
- taking paracetamol or ibuprofen half an
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Risk
What is known
Preventability
(arthralgia);
hour before a peginterferon beta-1a
- chills, feeling cold;
injection and continuing to take it for up
- fever;
to a day. Patients should speak with
- feeling weak and tired (asthenia).
their doctor or pharmacist about a
Flu-like symptoms are more common
suitable dose.
when patients first start using
- drinking plenty of water to stay
peginterferon beta-1a. They gradually
hydrated if they develop a fever.
get less frequent as a patient keeps using peginterferon beta-1a. Depression,
Depression has been seen in less than 1
If patients experience any of the
suicidal
in 10 people during treatment with
following:
behaviour
Plegridy.
- 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.
Seizures (fits or
MS increases the chance that a patient
Plegridy should be administered with
convulsions)
can develop fits or seizures. Seizures
caution to patients with a history of
were seen in less than 1 in 100 people
seizures and to those receiving
taking Plegridy.
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.
Thyroid
Patients with MS have an increased
The doctor may do blood tests from time
disorders
chance of developing thyroid disorders,
to time to make sure that a patient’s
particularly an underactive thyroid. This
thyroid function is normal. Patients with
risk may be even higher in patients
thyroid problems should talk to their
taking peginterferon beta-1a.
doctor, pharmacist, or nurse before injecting peginterferon beta-1a.
Important potential risks Risk
What is known
Cardiac (heart)
Worsening of cardiac disease has been reported in patients receiving
disorders
interferon beta. If patients develop heart problems, which can cause symptoms such as chest pain (angina), particularly after any activity; swollen Page 3/6
Risk
What is known 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.
Cancer
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.
Immunogenicity
Antibodies against peginterferon beta-1a were seen in less than 1% of
(ability of a substance
patients treated with Plegridy. These antibodies had no effect on the safety or
to provoke an
efficacy of peginterferon beta-1a.
immune response) Systemic lupus
Patients with SLE, a disease where the immune system attacks the body’s own
erythematosus (SLE)
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.
Thrombotic
Cases (including fatal cases) of TMA, a rare and serious condition associated
microangiopathies
with the formation of blood clots in the small blood vessels, have been
(TMAs) including
reported with interferon beta products indicated for the treatment of MS.
thrombocytopenic
There were no reported cases of TMA from the main studies with Plegridy in
purpura (TTP) and
patients with MS.
haemolytic uraemic syndrome (HUS) Nephrotic syndrome /
Cases of various kidney disorders resulting in nephrotic syndrome (abnormal
glomerulosclerosis
function of the kidney leading to loss of protein in the urine and fluid build-up
(kidney disorders)
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
What is known
Use in paediatric patients
Plegridy has not been studied in patients under 18 years of age.
Use in older patients
Plegridy has not been studied in patients over 65 years of age.
Effects on pregnancy and use in breastfeeding women
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.
Use in patients with hepatic impairment (reduced liver function)
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
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Risk
What is known 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
Safety in patients with decreased peripheral blood counts
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.
Drug-drug interaction
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)
Objectives
Safety concerns /efficacy issue addressed
Status
Planned date for submission of (interim and) final results
Paediatric study
How safe, well
Growth (height,
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
European
To evaluate
To address
Started with
PSURs sent to
Interferon Beta
pregnancy
findings from
premarketing
regulators. In
Pregnancy
outcomes,
experimental
clinical trials and
Europe, an annual
Registry
including
studies of
will continue
report is
frequency of
spontaneous
post-marketing.
submitted with
spontaneous
abortions in
combined data
abortion, and
monkeys receiving
from all marketing
frequency of birth
high doses of non-
authorisation
defects.
pegylated1
holders enrolled in
interferon
the registry.
beta-1a. Phase 3 Extension
To assess how
Clinical safety
Study, 105MS302
effective, safe,
tests, tests for
and well tolerated
depression,
peginterferon
changes in
beta-1a is in
laboratory values,
subjects originally
and
treated in Study
immunogenicity.
Ongoing
Final report by March 2016
105MS301 who continue peginterferon beta-1a treatment.
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 01-2016.
1
This document has been updated; the previous version referred to ‘peginterferon beta-1a’.
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