THE OPTIMIZATION OF INTERFERON FOR MS STUDY: 375 MICROG INTERFERON BETA-1B IN SUBOPTIMAL RESPONDERS.
- Autori: Durelli L; Barbero P; Verdun E; Ferrero B; Clerico M; Ricci A; Cucci A; Contessa G; Rivoiro C; Ferrero C; Picco E; Ripellino P; Viglietti D; Bergui M; Zhong JJ; Versino E; Rottoli M; Moroni S; Teatini F; Schoenhuber R; Spissu A; Reggio A; Lo Fermo S; Liberto A; Perla F; Grasso E; Montanari E; Pesci I; Manneschi L; Ghezzi A; Zaffaroni M; Carolei A; Totaro R; Giuliani G; Pucci E; Cartechini E; Scarpini E; Clerici R; Protti A; Erminio C; Cotrufo R; Lus G; Savettieri G; Salemi G; Bergamaschi R; Romani A; Bassano MA; Policreti A; Iudice A; Frittelli C; Motti L; Marcello N; Meola G; Robotti M; Cavallo R; Ravetti C; Deotto K
- Anno di pubblicazione: 2008
- Tipologia: Articolo in rivista (Articolo in rivista)
- Parole Chiave: multiple sclerosis; interferon beta (IFNβ); immunomodulatory drugs; MRI activity; suboptimal treatment response
- OA Link: http://hdl.handle.net/10447/49084
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.