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
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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.
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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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