USE IN SPECIFIC POPULATIONS

Pregnancy

Epidemiological data do not suggest a clear relationship between interferon beta use and major congenital malformations, but interferon beta may cause fetal harm based on animal data  

Risk Summary

Data from a large population-based cohort study, as well as other published studies over several decades, have not identified a drug-associated risk of major birth defects with the use of interferon beta products during early pregnancy.

Findings regarding a potential risk for low birth weight or miscarriage with the use of interferon beta products in human pregnancy have been inconsistent (see Human Data). In a study in pregnant monkeys, administration of interferon beta during pregnancy resulted in an increased rate of abortion (see Animal Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Human Data

In a population-based cohort study conducted in Finland and Sweden, data were collected from 1996–2014 in Finland and 2005–2014 in Sweden on 2,831 pregnancy outcomes from women with MS. 797 pregnancies were in women exposed to interferon beta only. No evidence was found of an increased risk of major birth defects among women with MS exposed to interferon beta products compared to women with MS that were unexposed to any non-steroid therapy for MS (n=1,647) within the study. No increased risks were observed for miscarriages and ectopic pregnancies, though there were limitations in obtaining complete data capture for these outcomes, making the interpretation of the findings more difficult.

Two small cohort studies that examined pregnancies exposed to interferon beta products (without differentiating between subtypes of interferon beta products) suggested that a decrease in mean birth weight may be associated with interferon beta exposure during pregnancy, but this finding was not confirmed in larger observational studies. Two small studies observed an increased prevalence of miscarriage, although the finding was only statistically significant in one study. Most studies enrolled patients later in pregnancy, which made it difficult to ascertain the true percentage of miscarriages. In one small cohort study, a significantly increased risk of preterm birth following interferon beta exposure during pregnancy was observed.

Animal Data

PLEGRIDY has not been tested for developmental toxicity in pregnant animals. In monkeys given interferon beta by subcutaneous injection every other day during early pregnancy, no adverse effects on embryofetal development were observed. Abortifacient activity was evident following 3 to 5 doses.

Lactation

Risk Summary

For PLEGRIDY patients considering breastfeeding, limited published literature has described the presence of interferon beta-1a products in human milk at low levels. There are no data on the effects of interferon beta-1a on milk production. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for PLEGRIDY and any potential adverse effects on the breastfed infant from PLEGRIDY or from the underlying maternal condition.

Advise patients to notify their healthcare provider if they become pregnant during treatment or plan to become pregnant.

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PLEGRIDY during pregnancy. Encourage patients who become pregnant while taking PLEGRIDY to enroll in the PLEGRIDY pregnancy registry by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com.

Please see full Prescribing Information.

Important Safety Information

CONTRAINDICATIONS

  • PLEGRIDY® (peginterferon beta-1a) is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta or peginterferon, or any other component of the formulation

WARNINGS AND PRECAUTIONS

Hepatic Injury

  • Severe hepatic injury, including hepatitis, autoimmune hepatitis, and rare cases of severe hepatic failure, have been reported with interferon beta. Asymptomatic elevation of hepatic transaminases has also been reported, and in some patients has recurred upon rechallenge with interferon beta. Elevations in hepatic enzymes and hepatic injury have been observed with PLEGRIDY in clinical studies. Monitor liver function tests and patients for signs of hepatic injury. Consider discontinuation of PLEGRIDY if hepatic injury occurs

Depression and Suicide

  • Depression, suicidal ideation, and suicide occur more frequently in patients receiving interferon beta than in patients receiving placebo. Advise patients to report immediately any symptom of depression or suicidal ideation. If a patient develops depression or other severe psychiatric symptoms, consider stopping treatment with PLEGRIDY

Seizures

  • Seizures are associated with the use of interferon beta. The incidence of seizures in clinical studies was less than 1% in patients receiving PLEGRIDY and placebo. Exercise caution when administering PLEGRIDY to patients with a seizure disorder

Anaphylaxis and Other Allergic Reactions

  • Anaphylaxis and other serious allergic reactions are rare complications of treatment with interferon beta. Less than 1% of PLEGRIDY-treated patients experienced a serious allergic reaction such as angioedema or urticaria. Discontinue PLEGRIDY if a serious allergic reaction occurs

Injection Site Reactions

  • Injection site reactions, including injection site necrosis, can occur with the use of subcutaneous interferon beta. The incidence of injection site reactions (e.g., injection site erythema, pain, pruritus, or edema) was 66% in the PLEGRIDY group (3% were severe) and 11% in the placebo group (0% were severe). One patient out of 1468 patients who received PLEGRIDY experienced injection site necrosis. Decisions to discontinue therapy following necrosis at a single injection site should be based on the extent of the necrosis. If therapy is continued, avoid administration of PLEGRIDY near the affected area until it is fully healed. If multiple lesions occur, discontinue PLEGRIDY until healing occurs

Congestive Heart Failure

  • Congestive heart failure, cardiomyopathy, and cardiomyopathy with congestive heart failure occur in patients receiving interferon beta. The incidence of cardiovascular events was 7% in both PLEGRIDY and placebo treatment groups. Monitor patients with significant cardiac disease for worsening of their cardiac condition during initiation and continuation of treatment with PLEGRIDY

Decreased Peripheral Blood Counts

  • Interferon beta can cause decreased peripheral blood counts in all cell lines, including rare instances of pancytopenia and severe thrombocytopenia. Decreases in white blood cell counts below 3.0 x 109/L occurred in 7% of patients receiving PLEGRIDY and in 1% receiving placebo. The incidence of clinically significant decreases in lymphocyte counts (below 0.5 x 109/L), neutrophil counts (below 1.0 x 109/L), and platelet counts (below 100 x 109/L) were all less than 1% and similar in both placebo and PLEGRIDY groups. Monitor patients for infections, bleeding, and symptoms of anemia. Monitor complete blood cell counts, differential white blood cell counts, and platelet counts during treatment with PLEGRIDY. Patients with myelosuppression may require more intensive monitoring of blood cell counts

Thrombotic microangiopathy

  • Cases of thrombotic microangiopathy (TMA), including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, some fatal, have been reported several weeks to years after starting interferon beta products. Discontinue PLEGRIDY if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated

Autoimmune disorders

  • Autoimmune disorders of multiple target organs including idiopathic thrombocytopenia, hyper- and hypothyroidism, and autoimmune hepatitis have been reported with interferon beta. The incidence of autoimmune disorders was less than 1% in both PLEGRIDY and placebo treatment groups. If patients develop a new autoimmune disorder, consider stopping PLEGRIDY

MOST COMMON SIDE EFFECTS

  • The most common adverse reactions (incidence greater than 10% and at least 2% more than placebo) associated with PLEGRIDY treatment are injection site erythema, influenza-like illness, pyrexia, headache, myalgia, chills, injection site pain, asthenia, injection site pruritus, and arthralgia

PREGNANCY

  • There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PLEGRIDY during pregnancy
  • Encourage patients who become pregnant while taking PLEGRIDY to enroll in the PLEGRIDY pregnancy registry by calling 1-866-810-1462 or visiting https://www.plegridypregnancyregistry.com

Please see full Prescribing Information.

Indication

PLEGRIDY® (peginterferon beta-1a) is an interferon beta indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Reference: 1. PLEGRIDY Prescribing Information. Cambridge, MA: Biogen.