MRI activity and neutralising antibody as predictors of response to interferon beta treatment in multiple sclerosis

We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFN beta-1b) 375 mu g (subcutaneously [sc] every other day [eod]) in relapsing-remitting multiple sclerosis (RRMS) patients with a suboptimal response to IFN beta-1b 250 mu g, i.e., with MRI activity or relapses. The OPTimization of Interferon for MS (OPTIMS) study was a prospective multicenter randomized phase 2 trial comprising a 6-month run-in phase (to identify suboptimal responders) and a 6-month randomized phase of open-label clinical and blinded MRI follow-up. During run-in all patients were treated with IFN beta-1b 250 mu g sc eod; during the study phase suboptimal treatment responders were randomized either to IFN mu-1b 250 or 375 mu g sc eod. Primary outcome was the proportion of patients without MRI activity during study Months 9-12 according to the intention-to-treat principle. 216 RRMS patients entered the study: 83 suboptimal responders were identified and randomized, 7 refused to continue treatment, 76 were included in the analysis. More patients treated with 375 mu g had no MRI activity at Months 9-12 (30/36 vs. 16/40; relative risk, 0.28; 95 % confidence interval, 0.08-0.47; p = 0.0001). Sensitivity analysis ("worst case scenario") confirmed the results. No new or nexpected adverse events were observed, but there was a trend towards more withdrawals in the 375 mu g group. Increasing the dose of IFN beta-1b from 250 mu g to 375 mu g is a successful strategy for reducing subclinical signs of disease activity in RRMS patients. Further studies are needed to show whether this dose may also improve clinical efficacy.