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Rebif demonstrated a significant reduction in MRI lesions1,2

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  • In PRISMS, patients on Rebif showed a 78% reduction in T2 active lesions vs placebo after 2 years1,2
    • Median number of T2 active lesions per patient per scan was 0.5 for 44 mcg (n=172) vs 2.25 for placebo (n=171); P<0.0001

Significant CUA lesion reduction as early as 2 months and sustained up to 9 months of observation1,2

Monthly scans: mean number of CUA lesions through 9 months vs placebo*,†,‡

  • Placebo
    (n=66)
  • Rebif
    (interferon beta-1a)
    22 mcg SC tiw
    (n=64)
    P=0.00654
  • Rebif
    44 mcg SC tiw
    (n=68)
    P=0.0008

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

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

AT 2 MONTHS:

  • There was a significant reduction in CUA lesions (ie, lesions with either T1-Gd+ or PD/T2 activity with Rebif compared with placebo, which was evident at 2 months (P=0.0065 and 0.0008 for the 22-mcg and 44-mcg groups, respectively)
  • There was a 42% reduction in percent combined active scans per patient with Rebif 44 mcg vs placebo (32% vs 55%, respectively: P=0.0008)

AT 9 MONTHS:

  • There was a 62% reduction in percent combined active scans per patient with Rebif 44 mcg vs placebo (19% vs 50%, respectively: P<0.0001)
    • Plotting these data over time showed that progressive accumulation of lesions was blunted in Rebif patients compared with placebo, with a nonsignificant trend toward greater effect in the 44-mcg compared with the 22-mcg group

Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis (PRISMS) was a double-blind, placebo-controlled study conducted over 2 years. Patients were randomly assigned Rebif 44 mcg (n=184), Rebif 22 mcg (n=189), or placebo (n=187), given 3 times weekly by subcutaneous injection. Outcomes measured included relapse rate, disability, MRI, safety, and antigenicity. Neurological assessments were conducted every 3 months.

*From a subgroup of 205 patients who underwent monthly MRI scans for the first 9 months, intent-to-treat population had biannual scans.

PD/T2 lesion load also decreased significantly compared with placebo1

Decreased PD/T2 lesion load: biannual scans

  • Placebo
    (n=187)
  • Rebif
    22 mcg SC tiw (n=189)
  • Rebif
    44 mcg SC tiw (n=184)
  • *P=0.0246 44 mcg vs 22 mcg, not significant at subsequent time points.
    P<0.0001 vs placebo.

Lesion load is defined as the total area of lesions in the brain measured in mm2. PD: proton density.

  • Both Rebif groups exhibited a decrease in T2 lesion load, which was evident by 6 months of observation; at 2 years, there was a 1.2% and 3.8% reduction in the 22-mcg and 44-mcg groups, respectively (P<0.0001 compared with placebo for each group); at 6 months, the difference between the 22-mcg and 44-mcg groups was significant (P=0.0246) but was not significant at subsequent time points, although the trend favored the higher dose

Significant reductions in T1-Gd+ lesions at 9 months

Significant reductions in T1-Gd+ lesions*,‡ at 9 months

*From a subgroup of 205 patients who underwent monthly MRI scans for the first 9 months, intent-to-treat population had biannual scans.

Proportion of scans per patient per treatment group with new activity, including new, enlarging, recurrent PD/T2 lesions or enhancing T1 lesions.

Analysis of the subgroup of patients undergoing PD/T2 and T1-Gd+ MRI scans at prestudy screening, study day 1, and monthly for the first 9 months of treatment based on ANOVA on the ranks taking center and number of active lesions at baseline into account.

PRISMS STUDY DESIGN +

PRISMS1 trial: initiated in 1994

  STUDY DESIGN TREATMENT GROUPS CLINICAL ASSESSMENTS OUTCOMES MEASURED INCLUDED

2 years

Double-blind, placebo-controlled study (class 1)

Rebif 44 mcg
SC tiw (n=184)

Rebif 22 mcg
SC tiw (n=189)

Placebo (n=187)

Every 3 months

–Relapse rate
(primary endpoint)

–Disability progression

–MRI outcomes

–Safety

–Antigenicity

Prevention of Relapses and Disability by Interferon β-1a Subcutaneously in Multiple Sclerosis (PRISMS) was a double-blind, placebo-controlled study conducted over 2 years. Patients were randomly assigned Rebif 44 mcg (n=184), Rebif 22 mcg (n=189), or placebo (n=187), given 3 times weekly by subcutaneous injection. Outcomes measured included relapse rate, disability progression, MRI outcomes, safety, and antigenicity. Neurological assessments were conducted every 3 months.

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. Li DKB, Paty DW, UBC MS/MRI Analysis Research Group, PRISMS Study Group. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-β1a in relapsing-remitting multiple sclerosis. Ann Neurol. 1999;46(2):197-206. 2. Data on file. EMD Serono, Inc. 3. PRISMS Study Group. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet. 1998;352(9139):1498-1504.

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

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