BackgroundInterferon &bgr; (IFN&bgr;) reduces relapses and MRI activity in relapsing-remitting MS (RRMS), with variable effects on disability. The most effective dose regimen remains controversial. MethodsThis randomized, controlled, multicenter trial compared the efficacy and safety of IFN&bgr;-1a (Rebif®) 44 &mgr;g subcutaneously three times weekly (tiw), and IFN&bgr;-1a (Avonex®) 30 &mgr;g 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. ResultsAfter 24 weeks, 74.9% (254/339) of patients receiving IFN&bgr;-1a 44 &mgr;g tiw remained relapse free compared with 63.3% (214/338) of those given 30 &mgr;g 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 &mgr;g tiw. Patients receiving 44 &mgr;g tiw had fewer active MRI lesions (p < 0.001 at 24 and 48 weeks) compared with those receiving 30 &mgr;g qw. Injection-site reactions were more frequent with 44 &mgr;g 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 &mgr;g qw dosage. Neutralizing antibodies developed in 25% of 44 &mgr;g tiw patients and in 2% of patients receiving 30 &mgr;g qw. ConclusionsIFN&bgr;-1a 44 &mgr;g subcutaneously tiw was more effective than IFN&bgr;-1a 30 &mgr;g IM qw on all primary and secondary outcomes investigated after 24 and 48 weeks of treatment.