Randomized, comparative study of interferon β-1a treatment regimens in MS -: The EVIDENCE trial

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