H. Panitch, MD, D.S. Goodin, MD, G. Francis, MD, P. Chang, PhD, P.K. Coyle, MD, P. OíConnor, MD, E. Monaghan, PhD, D. Li, MD and B. Weinshenker, MD for the EVIDENCE (EVidence of Interferon Dose-response: European North American Comparative Efficacy) Study Group and the University of British Columbia MS/MRI Research Group
University of Vermont College of Medicine (Dr. Panitch), Burlington; University of California (Dr. Goodin), San Francisco; University Hospital Medical Center (Dr. Coyle), State University of New York at Stony Brook; Mayo Clinic (Dr. Weinshenker), Rochester, MN; St. Michaelís Hospital (Dr. OíConnor), University of Toronto, Canada; University of British Columbia (Dr. Li), Vancouver, Canada; and Serono Inc. (Drs. Francis, Chang, and Monaghan), Rockland, MA
Interferon ß (IFNß) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial.
This randomized, controlled, multicenter trial compared the efficacy and safety of IFNß-1a (Rebif®) 44 µg subcutaneously three times weekly (tiw), and IFNß-1a (Avonex®) 30 µg IM once weekly (qw) in 677 patients with RRMS. Assessors blinded to treatment performed neurologic and MRI evaluations. The primary endpoint was the proportion of patients who were relapse free at 24 weeks; the principal MRI endpoint was the number of active lesions per patient per scan at 24 weeks.
After 24 weeks, 74.9% (254/339) of patients receiving IFNß-1a 44 µg tiw remained relapse free compared with 63.3% (214/338) of those given 30 µg qw. The odds ratio for remaining relapse free was 1.9 (95% CI, 1.3 to 2.6; p = 0.0005) at 24 weeks and 1.5 (95% CI, 1.1 to 2.1; p = 0.009) at 48 weeks, favoring 44 µg tiw. Patients receiving 44 µg tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 µg qw. Injection-site reactions were more frequent with 44 µg tiw (83% vs 28%, p < 0.001), as were asymptomatic abnormalities of liver enzymes (18% vs 9%, p = 0.002) and altered leukocyte counts (11% vs 5%, p = 0.003) compared with the 30 µg qw dosage. Neutralizing antibodies developed in 25% of 44 µg tiw patients and in 2% of patients receiving 30 µg qw.
IFNß-1a 44 µg subcutaneously tiw was more effective than IFNß-1a 30 µg IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.
© 2002 American Academy of Neurology