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In EVIDENCE, Rebif was superior to Avonex® in MRI and relapse clinical measures1,2

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Rebif was superior to Avonex (interferon beta-1a) in reducing CUA lesions and T2 lesion load1

  • Maximum effect observed within 2 to 3 months of starting Rebif

EVIDENCE: Reductions in CUA lesions over 24 weeks THROUGH
MONTH 6

CUA: combined unique active, defined as any lesion that was T1 active or T2 active.

  • Fewer CUA lesions per patient per scan during first 24 weeks of treatment (P<0.001)
  • At 48 weeks, a 36% relative reduction in mean number of T2 lesions per patient per scan in patients taking Rebif vs Avonex (P<0.001)

The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

Rebif reduced the risk of relapse by 30% compared with Avonex2*

Risk of relapse over an average of 64 weeks* 30% REDUCED
RISK OF RELAPSE

*The 40th percentile time to first exacerbation was 13.5 months for Rebif-treated patients and 6.7 months for Avonex-treated patients, demonstrating a delay in first exacerbation of approximately 6.8 months in favor of Rebif for the 40th percentile patients.

  • The greatest separation of the survival curves was achieved in the first 24 weeks of treatment

EVidence of Interferon Dose-response: European North American Comparative Efficacy (EVIDENCE) was an assessor-blinded, parallel-group study conducted over an average of 64 weeks. Patients were randomized to receive Rebif 44 mcg subcutaneously 3 times weekly (n=339) or Avonex 30 mcg intramuscularly once weekly (n=338). Outcomes measured included percentage relapse free, MRI, safety, and antigenicity and were determined at 24, 48, and an average of 64 weeks.

The extension phase of the EVIDENCE study was an open-label, within-treatment-group comparison of patients who elected to remain in the study and take Rebif 44 mcg subcutaneously 3 times weekly (n=272) for an average of 8 months versus their final 6 months on Avonex intramuscularly (n=223). Outcomes measured included relapses, MRI, safety, and antigenicity. Patients were followed for an average of 8 months.

Rebif provided ongoing relapse reductions in the EVIDENCE extension phase2

Patients who had been on Avonex for 6 months and transitioned to Rebif had a 50% reduction in relapse rate at an average of 8 months posttransition

Transitioned from Avonex to Rebif (n=223)

The extension phase of the EVIDENCE study was an open-label, within-treatment-group comparison of patients who elected to remain in the study and take Rebif 44 mcg subcutaneously 3 times weekly (n=272) for an average of 8 months vs their final 6 months on Avonex intramuscularly (n=223). Outcomes measured included relapses, MRI, safety, and antigenicity. Patients were followed for an average of 8 months.

Of the 605 patients receiving therapy at the end of the comparative phase of EVIDENCE, 495 patients enrolled in the extension phase of the study. In the extension phase, all patients were offered the option of either taking Rebif 44 mcg 3 times weekly or leaving the study. Clinical assessments were not blinded, but MRI evaluations were blinded. All assessments were within-treatment-group comparisons. Patients were followed for an average of 8 months posttransition. Annualized relapse rate is based on a time-adjusted analysis.

The EVIDENCE study does not support any conclusion regarding any effects on the accumulation of disability.

EVIDENCE STUDY DESIGN +

EVIDENCE trial: initiated in 1999

  STUDY DESIGN TREATMENT GROUPS CLINICAL ASSESSMENTS OUTCOMES MEASURED

Comparative phase (64-week average)

Randomized, assessor-blinded, parallel-group, superiority study (class I)

Rebif (interferon beta-1a) 44 mcg SC tiw (n=339)

Avonex® (interferon beta-1a) 30 mcg IM qw (n=338)

Efficacy outcomes determined at 24, 48, and an average of 64 weeks

–Percent relapse-free (primary endpoint)

–MRI outcomes

–Safety

–Antigenicity

–Disability progression

Extension phase

Open-label, within-treatment-group comparison of patients who elected to change therapy to Rebif vs final 6 months on Avonex therapy

Rebif 44 mcg SC tiw (n=272)

Avonex IM qw (n=223)

Patients were followed for an average of 8 months

–Relapses

–MRI outcomes

–Safety

–Antigenicity

Class I clinical trials are prospective, randomized, controlled, blinded trials with clearly defined primary outcomes and inclusion/exclusion criteria.

INDICATION

Rebif is indicated for the treatment of patients with relapsing forms of MS to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability.

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.

There are no adequate and well-controlled studies in pregnant women. Rebif should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INDICATION

Rebif is indicated for the treatment of patients with relapsing forms of MS to decrease the frequency of clinical exacerbations and delay the accumulation of physical disability.

Please see Rebif Prescribing Information and Medication Guide.

References: 1. Panitch H, Goodin DS, Francis G, et al; EVIDENCE Study Group and the University of British Columbia MS/MRI Research Group. Randomized, comparative study of Interferon β-1a treatment regimens in MS: the EVIDENCE trial. Neurology. 2002;59(10):1496-1506. 2. Schwid SR, Panitch HS. Full results of the Evidence of Interferon Dose-Response-European North American Comparative Efficacy (EVIDENCE) study: a multicenter, randomized, assessor-blinded comparison of low-dose weekly versus high-dose, high-frequency interferon β-1a for relapsing multiple sclerosis. Clin Ther. 2007;29(9):2031-2048.

Rebif and MS LifeLines are registered trademarks of EMD Serono, Inc. or its affiliates. Avonex is a registered trademark of Biogen.

©2017 EMD Serono, Inc. All rights reserved. US/REB/0217/0042(1) 07/17