Safety profile

 

Image with text that says - 20+ YEARS of combined trial and real-world evidence RESULTING IN WELL-ESTABLISHED SAFETY PROFILE

 

  • In clinical trials, Rebif® did not result in increases in the incidence of viral, bacterial, or fungal infections1
  • The US Prescribing Information notes that patients may be more likely to get infections due to decreased peripheral blood counts2
  • No PML has been associated with Rebif®2
  • No restrictions on vaccinations are noted in the prescribing information (PI) for Rebif®.2 Use your clinical judgment and refer to CDC and other current guidelines regarding vaccination
  • 145 thousand+ US patients prescribed since approval3

Rebif® can cause serious adverse reactions

  • Depression, suicidal ideation, and suicide attempts
  • Severe liver injury including some cases of hepatic failure requiring liver transplantation
  • Anaphylaxis and other allergic reactions, some severe
  • Injection-site reactions
  • Decreased peripheral blood counts in all cell lines
  • Cases of thrombotic microangiopathy (TMA), some fatal
  • Seizures

Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in Rebif®-treated patients.

In controlled clinical trials, leukopenia occurred at a higher frequency in Rebif®-treated patients than in placebo and Avonex®-treated patients. Thrombocytopenia and anemia occurred more frequently in 44 mcg Rebif®-treated patients than in placebo-treated patients. Patients should be monitored for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended.

The most common side effects with Rebif® are injection-site disorders, headaches, influenza-like symptoms, abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities.

Most frequently reported AEs in the PRISMS trial2

The following adverse reactions were reported in the PRISMS study for Rebif® 44 mcg and Rebif® 22 mcg vs placebo:

  • Injection-site reactions (92% and 89% vs 39%)
  • Headache (70% and 65% vs 63%)
  • Influenza-like symptoms (59% and 56% vs 51%)
  • Abdominal pain (20% and 22% vs 17%)
  • SGPT increased (27% and 20% vs 4%)
  • SGOT increased (17% and 10% vs 4%)
  • Leukopenia (36% and 28% vs 14%)

 

In the PRISMS study:

  • Patients treated with Rebif® showed a similar incidence of infections compared to placebo1.
  • Rebif® did not result in increases in the incidence of viral, bacterial, or fungal infections1
  • The USPI notes that patients may be more likely to get infections due to decreased peripheral blood counts2

EVIDENCE trial (Rebif® 44 mcg vs Avonex®)4

Adverse reactions in the EVIDENCE study were generally similar to those in the PRISMS study.

Compared with Avonex®, adverse events were similar over an average of 64 weeks, despite higher, more frequent dosing with Rebif®. Exceptions include (Rebif® vs Avonex®):

  • Injection-site disorders (85% vs 33%)
  • Hepatic function disorders (18% vs 10%)
  • White blood cell disorders (14% vs 5%)
  • Flu-like symptoms (45% vs 53%)

AE: adverse event; PML: progressive multifocal leukoencephalopathy; SGOT: serum glutamic oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase.


IMPORTANT SAFETY INFORMATION AND INDICATION

Important Safety Information

Rebif is contraindicated in patients with a history of hypersensitivity to natural or recombinant interferon beta, human albumin, or any other component of the formulation.

Rebif should be used with caution in patients with depression, a condition that is common in people with multiple sclerosis. Depression, suicidal ideation, and suicide attempts have been reported to occur with increased frequency in patients receiving interferon compounds, including Rebif.

Severe liver injury, including some cases of hepatic failure requiring liver transplantation, has been reported rarely in patients taking Rebif. The potential for liver injury should be considered when used in combination with other products associated with liver injury. Monitor liver function tests and patients for signs and symptoms of hepatic injury. Consider discontinuing Rebif if hepatic injury occurs.

Anaphylaxis and other allergic reactions (some severe) have been reported as a rare complication of Rebif. Discontinue Rebif if anaphylaxis occurs.

In controlled clinical trials, injection site reactions occurred more frequently in Rebif-treated patients than in placebo-treated and Avonex-treated patients. Injection site reactions including injection site pain, erythema, edema, cellulitis, abscess, and necrosis have been reported in the postmarketing setting. Do not administer Rebif into affected area until fully healed; if multiple lesions occur, discontinue Rebif until skin lesions are healed.

Decreased peripheral blood counts in all cell lines, including pancytopenia, have been reported in Rebif-treated patients. In controlled clinical trials, leukopenia occurred at a higher frequency in Rebif-treated patients than in placebo and Avonex-treated patients. Thrombocytopenia and anemia occurred more frequently in 44 mcg Rebif-treated patients than in placebo-treated patients. Patients should be monitored for symptoms or signs of decreased blood counts. Monitoring of complete blood and differential white blood cell counts is also recommended.

Cases of thrombotic microangiopathy (TMA), some fatal, have been reported with interferon beta products, including Rebif, up to several weeks or years after starting therapy. Discontinue Rebif if clinical symptoms and laboratory findings consistent with TMA occur, and manage as clinically indicated.

Caution should be exercised when administering Rebif to patients with pre-existing seizure disorders. Seizures have been temporally associated with the use of beta interferons, including Rebif, in clinical trials and in postmarketing reports.

The most common side effects with Rebif are injection-site disorders, headaches, influenza-like symptoms, abdominal pain, depression, elevated liver enzymes, and hematologic abnormalities.

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 studies. Data from a large human 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 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 pregnancy have been inconsistent.

Indication

Rebif is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Please see Rebif® Prescribing Information  and Medication Guide.

 

References: 1. Data on file. EMD Serono, Inc. PRISMS study report. 2. Rebif® [Prescribing Information]. Rockland, MA: EMD Serono, Inc. 3. Data on file. EMD Serono, Inc. NS/RS patients through MS LifeLines®. 4. Panitch H, Goodin D, Francis G, et al; for EVIDENCE (EVidence of Interferon Dose-response-European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group. Benefits of high-dose, high-frequency interferon beta-1a in relapsing-remitting multiple sclerosis are sustained to 16 months: final comparative results of the EVIDENCE trial. J Neurol Sci. 2005;239(1):67-74.