Impact of early interferon beta-1b treatment on disease evolution over five years in patients with a first event suggestive of multiple sclerosis

Background: TheBENEFITstudy(BEtaseron ® /BEtaferon ® inNewlyEmergingMS For Initial Treatment) was designed to evaluate the impact of early treatment initiationwithinterferonbeta-1b(IFNB-1b;Betaseron ® /Betaferon ® )inpatients withafirsteventsuggestiveofmultiplesclerosis(MS). Objective: Topresentthe5-yearresults. Methods: Intheplacebo-controlledphase,patientswererandomizedtoIFNB-1b 250 µg or placebo, subcutaneously every other day, for 2 years or until clinicallydefiniteMS(CDMS),ifearlier.Patientscouldthenenrollinafollow-up phase and were offered, but not required to take, IFNB-1b. Patients and physicians remained blinded to the initial treatment allocation. Patients initially randomized to IFNB-1b are defined as 'early-treatment' group and thoseinitiallyrandomizedtoplaceboas'delayedtreatment'.Primaryoutcome measuresincludedtimetoCDMSandtimetoconfirmeddisabilityprogression, measured by the Expanded Disability Status Scale (EDSS). Analyses were prospectively planned at 3 and 5 years using a predefined hierarchical statisticalanalysisplan. Results: Ofthe468patientsoriginallyrandomized(IFNB-1b:292,placebo:176), 358 (76%) were followed for 5 years. In line with the 3-year analysis, early treatment with IFNB-1b versus delayed treatment reduced the risk of developingCDMSby37%over5years( p=0.003),andledtoanoverall20% reductioninrelapserate( p=0.014)aswellasasignificantreductioninnew lesion formation. Early treatment reduced the risk of confirmed EDSS progressionby40%( p=0.0218)at3years;therespectiveriskreductionwas 24%after5years,notreachingstatisticalsignificance.Qualityofliferemained high and stable over time in both groups.At 5 years ( p=0.0045), patients in the early-treatment group performed better in the Paced Auditory Serial AdditionTest(PASAT). Conclusions: The5-yearresultsoftheBENEFITstudyprovidefurtherevidence supporting early initiation of treatment with IFNB-1b in patients with a first eventsuggestiveofMS. T2 lesions at screening (Q1, Q3) (7.0, 38.5) (7.5, 36.5) (7.0, 39.0) (8.0, 37.0) Median number of 00 00 Gd+ lesions at screening (Q1, Q3) (0.0, 1.0) (0.0, 1.0) (0.0, 1.0) (0.0, 1.0)