The OPTimization of interferon for MS study: 375 microg 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.

• Authors: Luca Durelli, Pierangelo Barbero, Mauro Bergui, Elisabetta Versino, Marco A Bassano, Elisabetta Verdun, Bruno Ferrero, Chiara Rivoiro, Cinzia Ferrero, Elisabetta Picco, Paolo Ripellino, Daniela Viglietti, Giorgio Giuliani, Enrico Montanari, Marinella Clerico, OPTIMS Study Group
• Journal: Journal of neurology (J Neurol) Vol. 255 Issue 9 Pg. 1315-23 (Sep 2008) ISSN: 0340-5354 [Print] Germany
• PMID: 18825438 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Interferon beta-1b
• Interferon-beta

Topics

• Adjuvants, Immunologic (administration & dosage, adverse effects, therapeutic use)
• Adolescent
• Adult
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Follow-Up Studies
• Humans
• Injections, Subcutaneous
• Interferon beta-1b
• Interferon-beta (administration & dosage, adverse effects, therapeutic use)
• Magnetic Resonance Imaging (methods)
• Middle Aged
• Multiple Sclerosis, Relapsing-Remitting (diagnosis, drug therapy)
• Prospective Studies
• Single-Blind Method
• Time Factors
• Treatment Outcome
• Young Adult