Side Effects of Plegridy (peginterferon beta-1a)

Plegridy (peginterferon beta-1a) is a protein produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary Cells into which the human interferon beta genes have been introduced. It is used to treat multiple sclerosis (MS).

It differs from interferon beta-1a by having polyethylene glycol attached to the interferon molecules (peglated) that allow the interferon to remain in the body for longer times thus allowing less frequent dosing. Plegridy is designed to be identical to interferon beta that is naturally produced by various cells in the body. Plegridy has antiviral properties and plays a role in regulating the immune response.

The exact mechanism by which Plegridy works in the body to treat MS is not known. Plegridy does not cure MS but it helps decrease the number of flare-ups and slows the occurrence of some physical disability that occurs in the disease.

Plegridy works in the same way and has similar side effects as other interferon beta-1a products such as Avonex and Rebif. However, it is given every 14 days versus once weekly or 3 times per week injections.

Common side effects of Plegridy include

• injection site reactions,
• flu-like symptoms,
• headache,
• muscle aches,
• nausea,
• pain,
• fever,
• diarrhea, and
• infections.

Serious side effects of Plegridy include

• stomach pain,
• increased liver enzymes,
• blood disorders (including decreased red blood cells, white blood cells, and platelets),
• seizures,
• suicidal thoughts or actions,
• liver disease, and
• serious allergic and skin reactions.

Drug interactions of Plegridy include zidovudine or hydroxyurea, which may increase the risk of bone marrow suppression.

Use of Plegridy has not been adequately evaluated in pregnant women.

Due to the lack of conclusive safety data, Plegridy should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. 

It is unknown if Plegridy is excreted in breast milk. As many drugs enter breast milk and can potentially harm a nursing infant, Plegridy should be used cautiously in breastfeeding mothers.

The most common side effects of interferon beta-1a are:

• injection site reactions,
• flu-like symptoms,
• headache,
• muscle aches,
• nausea,
• pain,
• fever,
• diarrhea, and
• infections.

Flu-like symptoms are commonly experienced when patients first start taking interferon beta-1a. These symptoms can be managed with over-the-counter pain and fever reducers, and usually decrease or go away over time.

Stomach pain, an increase in liver enzymes, and blood disorders including a drop in the number of red blood cells, white blood cells, and platelets also occur.

Interferon beta-1a may also cause other serious side effects including seizures, suicidal thoughts or actions, liver disease, and serious allergic and skin reactions.

The following serious adverse reactions are discussed in more detail in other sections of labeling:

• Hepatic Injury
• Depression and Suicide
• Seizures
• Anaphylaxis and Other Allergic Reactions
• Injection Site Reactions
• Congestive Heart Failure
• Decreased Peripheral Blood Counts
• Thrombotic Microangiopathy
• Autoimmune Disorders

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Plegridy cannot be directly compared to rates in clinical trials of other drugs and may not reflect the rates observed in practice.

• In clinical studies (Study 1 and Study 2), a total of 1468 patients with relapsing multiple sclerosis received Plegridy for up to 177 weeks (41 months), with an overall exposure equivalent to 1932 person-years.
• A total of 1093 patients received at least 1 year, and 415 patients at least 2 years of treatment with Plegridy.
• A total of 512 and 500 patients, respectively, received Plegridy 125 micrograms every 14 days or every 28 days during the placebo-controlled phase of Study 1 (year 1).
• The experience in year 2 of Study 1 and in the 2-year safety extension study (Study 2) was consistent with the experience in the 1-year placebo-controlled phase of Study 1.
• In the placebo-controlled phase of Study 1, the most common adverse drug reactions for Plegridy 125 micrograms subcutaneously every 14 days were
  • injection site erythema,
  • influenza-like illness,
  • pyrexia,
  • headache,
  • myalgia,
  • chills,
  • injection site pain,
  • asthenia,
  • injection site pruritus, and
  • arthralgia (all had incidence more than 10% and at least 2% more than placebo).
• The most commonly reported adverse event leading to discontinuation in patients treated with Plegridy 125 micrograms subcutaneously every 14 days was influenza-like illness (in less than 1% of patients).

Table 2 summarizes adverse reactions reported over 48 weeks from patients treated in the placebo-controlled phase of Study 1 who received subcutaneous Plegridy 125 micrograms (n=512), or placebo (n=500), every 14 days.

Table 2: Adverse reactions in the 48-week placebo-controlled phase of Study 1 with an incidence 2% higher for Plegridy than for placebo

Immunogenicity

For therapeutic proteins, there is a potential for immunogenicity. In Study 1, fewer than 1% of patients treated with Plegridy every 14 days for 1 year developed neutralizing antibodies. Approximately 7% of Plegridy-treated patients developed antibodies to PEG.

The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Plegridy with the incidence of antibodies to other products may be misleading.

Flu-Like Symptoms

Influenza-like illness was experienced by 47% of patients receiving Plegridy 125 micrograms every 14 days and 13% of patients receiving placebo. Fewer than 1% of Plegridy-treated patients in Study 1 discontinued treatment due to flu-like symptoms.

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