Efficacy and tolerability of intramuscular interferon beta-la compared with subcutaneous interferon beta-1a in relapsing MS: results from PROOF

Objective: Benefits from interferon beta (IFN beta) treatment in patients with multiple sclerosis are affected by many factors, including sustained clinical efficacy, acceptable tolerability, adherence to therapy, and the development of neutralizing antibodies (NAbs). The Prospective and Retrospective Long-Term Observational Study of Avonex and Rebif (PROOF) was designed to compare the relative efficacy and tolerability of the two IFN beta-1a products for up to 5 years. Methods: PROOF compared the relative efficacy and tolerability of intramuscular (IM) IFN beta-1a (Avonex) 30 mu g once weekly (n = 69) and subcutaneous (SC) IFN beta-1a (Rebif) 44 mu g three times per week (n = 67). The duration of the retrospective portion of the study was 12-24 months. Due to slow enrollment, PROOF ended earlier than planned and the final duration of the prospective portion of the study was 6 months. Therefore, between 18 and 30 months of efficacy and tolerability data were available for analysis. Results: After controlling for baseline disability level, Expanded Disability Status Scale (EDSS) scores revealed no statistically significant differences between the treatment groups during the prospective portion of the study, with sustained disability progression similar in both groups (25.8% IM IFN beta-1a 30 mu g once weekly vs. 26.7% SC IFN beta-1a 44 mu g three times per week). Relapse rates were similar in the groups, as were MRI endpoints of brain parenchymal fraction, T1 lesion volume, T2 lesion volume, number of new/enlarging T2 lesions, and gadolinium-enhancing (Gd+) lesion volume and count. Treatment groups differed in frequency of NAbs, with 19% of patients treated with SIC IFN beta-1a 44 mu g three times per week NAb+ compared with none treated with IM IFN beta-1a 30 mu g once weekly. More NAb+ patients compared with NAb-patients had disability progression (40.0% vs. 27.8%, p = NS), new or enlarging T2 lesions at the end of treatment (63.6% vs. 40.7%, p 0.003), and Gd+ lesions after 12-24 months of treatment (36.4% vs. 15%, p = 0.001). The IFN beta-1a products had comparable tolerability. However, fewer patients treated with IM IFN beta-1a 30 mu g once weekly had injection-site reactions (2.9% vs. 6.0%). Limitations of this study include its design and sample size, both of which hinder detection of differences in efficacy between IFN beta-1a treatments. Conclusions: The results of the present study show that the two IFN beta-1a products have comparable efficacy and differing immunogenicity.