6533b86dfe1ef96bd12ca017

RESEARCH PRODUCT

THE OPTIMIZATION OF INTERFERON FOR MS STUDY: 375 MICROG INTERFERON BETA-1B IN SUBOPTIMAL RESPONDERS.

Durelli LBarbero PVerdun EFerrero BClerico MRicci ACucci AContessa GRivoiro CFerrero CPicco ERipellino PViglietti DBergui MZhong JjVersino ERottoli MMoroni STeatini FSchoenhuber RSpissu AReggio ALo Fermo SLiberto APerla FGrasso EMontanari EPesci IManneschi LGhezzi AZaffaroni MCarolei ATotaro RGiuliani GPucci ECartechini EScarpini EClerici RProtti AErminio CCotrufo RLus GBergamaschi RRomani ABassano MaPolicreti AIudice AFrittelli CMotti LMarcello NMeola GRobotti MCavallo RRavetti CDeotto K.Giovanni SavettieriGiuseppe Salemi

subject

Adultmedicine.medical_specialtyTime FactorsAdolescentInjections Subcutaneoussuboptimal treatment responseGastroenterologyDrug Administration Schedulelaw.inventionYoung AdultMultiple Sclerosis Relapsing-RemittingAdjuvants ImmunologicRandomized controlled triallawInternal medicinemedicineHumansSingle-Blind MethodProspective StudiesAdverse effectProspective cohort studyinterferon beta (IFNβ)immunomodulatory drugSubclinical infectionDose-Response Relationship Drugbusiness.industryInterferon beta-1bInterferon-betaMiddle AgedMagnetic Resonance ImagingConfidence intervalSurgeryClinical trialTreatment OutcomeNeurologyRelative riskmultiple sclerosiMRI activitySettore MED/26 - NeurologiaNeurology (clinical)businessFollow-Up StudiesInterferon beta-1b

description

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.

yearjournalcountryeditionlanguage
2008-01-01
10.1007/s00415-008-0879-6http://hdl.handle.net/10447/49084