title: 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.affiliation: Dipartimento di Scienze Cliniche, e Biologiche, Universita' di Torino, Divisione di Neurologia, Ospedale Universitario S. Luigi Gonzaga, Regione Gonzole, 10, 10043, Orbassano (Torino), Italy. luca.durelli@unito.it
authors.forename: Luca
authors.initials: L
authors.lastname: Durelli
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Barbero
authors.forename: Mauro
authors.initials: M
authors.lastname: Bergui
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Versino
authors.forename: Marco A
authors.initials: MA
authors.lastname: Bassano
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Verdun
authors.forename: Bruno
authors.initials: B
authors.lastname: Ferrero
authors.forename: Chiara
authors.initials: C
authors.lastname: Rivoiro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ferrero
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Picco
authors.forename: Paolo
authors.initials: P
authors.lastname: Ripellino
authors.forename: Daniela
authors.initials: D
authors.lastname: Viglietti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giuliani
authors.forename: Enrico
authors.initials: E
authors.lastname: Montanari
authors.forename: Marinella
authors.initials: M
authors.lastname: Clerico
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000068576:Interferon beta-1b; D016899:Interferon-beta