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

Background: Interferon β-1a (IFNβ-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNβ-1a is not known. Objective: To determine whether IFNβ-1a 60 μg IM once weekly is more effective than IFNβ-1a 30 μg 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 IFNβ-1a 30 μg (n = 402) or 60 μg (n = 400) IM once weekly for ≥36 months. The primary endpoint was disability progression, defined as time to a sustained increase of ≥1.0 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-μg dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60-μg group. The incidences of neutralizing antibodies (titers ≥ 20) were 2.3% in the 30-μg group and 5.8% in the 60-μg group. Conclusion: There was no difference between IFNβ-1a 30 μg and 60 μg IM in clinical or MRI measures.