The OPTimization of Interferon for MS Study: 375 μg interferon beta-1b in suboptimal responders

Abstract

We aimed to evaluate the safety and MRI efficacy of interferon beta-1b (IFNbeta-1b) 375 microg (subcutaneously [sc] every other day [eod]) in relapsing-remitting multiple sclerosis (RRMS) patients with a suboptimal response to IFNbeta-1b 250 microg, 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 IFNbeta-1b 250 microg sc eod; during the study phase suboptimal treatment responders were randomized either to IFNbeta-1b 250 or 375 microg 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 microg 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 unexpected adverse events were observed, but there was a trend towards more withdrawals in the 375 microg group. Increasing the dose of IFNbeta-1b from 250 microg to 375 microg 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.

The Multiple Sclerosis Summit: A Critical Appraisal to Improve the Management of MS

“…Exactly when to switch and which switch is most efficacious remains unclear, however. In the studies by Durelli et al 5 and Prosperini et al, 6 switching to a higher-dose IFN beta demonstrated improvement in MRI parameters but had less effect on relapse rates or disability measures. On the other hand, the studies by Caon et al 7 and Carra et al 9 did show some reduction in relapse rates when switching between IFN betas, albeit not as robust of an effect as when switching to another agent.…”

“…Two studies have evaluated the effects of increasing the IFN beta dose in patients with suboptimal response. The first of these studies was performed by Durelli et al 5 In this prospective, randomized, phase II trial of 216 RRMS patients, 76 suboptimal responders to SC IFN beta-1b 250 µg QOD were analyzed. Suboptimal response was defined based on magnetic resonance imaging (MRI) criteria, the presence of a relapse, and/or confirmed disease progression.…”

Multiple sclerosis therapeutics

“…The latest news on this subject comes from the BEYOND study, 3 which did not show any superiority of 500 g IFN␤-1b every other day over 250 g IFN␤-1b. It remains a matter of speculation whether further dose optimizations can improve clinical efficacy, 9 and it is also unclear whether such short-term effects have any long-term consequences.…”

Recognizing and treating suboptimally controlled multiple sclerosis: steps toward regaining command

“…Some indirect and direct evidence suggests that patients with suboptimal response to IFN may benefit from increasing the dose of IFN [42][43][44][45] . Other studies have shown that switching patients between first-line DMDs (IFN to GA and vice versa and from one IFN agent to another) reduced clinical disease activity in patients with suboptimally controlled MS, but these latter studies were small, observational, and uncontrolled 28,29,46 .…”