Randomized study of once-weekly interferon β-1a therapy in relapsing multiple sclerosis:: three-year data from the OWIMS study

Background: Once weekly interferon beta-1a for multiple sclerosis ( OWIMS) demonstrated modest, but significant, magnetic resonance imaging ( MRI) benefit of once- weekly ( qw) interferon ( IFN) beta-1a at 48 weeks, but no significant effect on relapses. Objective: An OWIMS extension permitted assessment of longer- term efficacy/ safety of qw IFN beta-1a in relapsing - remitting multiple sclerosis ( RRMS). Methods: Placebo patients were rerandomized to IFN beta-1a, 22 or 44 mcg qw, for two additional 48- week intervals. Primary outcome was MRI lesion activity. Relapse rate and other MRI measures were secondary outcomes. Results: After three years, median ( mean) T2 lesion count/ patient/ scan was 1.3 ( 2.6) for 44 mcg, 1.7 ( 3.3) for 22 mcg, 1.7 ( 3.4) for placebo/ 22 mcg, 2.0 ( 3.6) for placebo/ 44 mcg ( all differences not significant). Annualized relapse rates were lowest for 44 mcg ( 0.77) versus other groups ( 0.83 - 0.86, not significant). Persistent neutralizing antibodies did not affect relapse rates, but MRI active lesions were increased in antibody- positive patients receiving 44 mcg compared to antibody negative patients. Conclusions: In RRMS, once weekly IFN beta-1a, particularly 44 mcg, can induce a significant MRI, but not relapse, effect, compared with placebo. No significant dose effect was seen. In contrast to the significant effect observed with three- times- weekly dosing of subcutaneous IFN beta- 1a compared with placebo, this study confirms the lack of meaningful clinical benefit with once- weekly dosing.