A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS

Background: Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known. Objective: To determine whether IFNbeta-1a 60 mug IM once weekly is more effective than IFNbeta-1a 30 mug IM once weekly in reducing disability progression in relapsing MS. Methods: In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 mug (n = 402) or 60 mug (n = 400) IM once weekly for greater than or equal to36 months. The primary endpoint was disability progression, defined as time to a sustained increase of greater than or equal to1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression. Results: Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60-mug dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60-mug group. The incidences of neutralizing antibodies (titers greater than or equal to20) were 2.3% in the 30-mug group and 5.8% in the 60-mug group. Conclusion: There was no difference between IFNbeta-1a 30 mug and 60 mug IM in clinical or MRI measures