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Time course of clinical and neuroradiological effects of delayed‐release dimethyl fumarate in multiple sclerosis
Author(s) -
Kappos L.,
Giovani G.,
Gold R.,
Phillips J. T.,
Arnold D. L.,
Hotermans C.,
Zhang A.,
Viglietta V.,
Fox R. J.
Publication year - 2015
Publication title -
european journal of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 124
eISSN - 1468-1331
pISSN - 1351-5101
DOI - 10.1111/ene.12624
Subject(s) - medicine , glatiramer acetate , dimethyl fumarate , placebo , multiple sclerosis , odds ratio , gastroenterology , nuclear medicine , pathology , immunology , alternative medicine
Background and purpose Delayed‐release dimethyl fumarate ( DMF , also known as gastro‐resistant DMF ), demonstrated efficacy and safety in relapsing−remitting multiple sclerosis in the 2‐year, randomized, placebo‐controlled, phase 3 DEFINE and CONFIRM trials. A post hoc analysis of integrated data from DEFINE and CONFIRM was conducted to determine the temporal profile of the clinical and neuroradiological effects of DMF . Methods Eligible patients were randomized to receive placebo, DMF 240 mg twice ( BID ) or three times ( TID ) daily or glatiramer acetate ( GA ; reference comparator; CONFIRM only) for up to 96 weeks. Patients in the GA group were excluded from this analysis. Results A total of 2301 patients were randomized and received treatment with placebo ( n = 771) or DMF BID ( n = 769) or TID ( n = 761). DMF significantly reduced the annualized relapse rate beginning in weeks 0–12 ( BID , P = 0.0159; TID , P = 0.0314); the proportion of patients relapsed beginning at week 10 ( BID , P = 0.0427) and week 12 ( TID , P = 0.0451); and the proportion of patients with 12‐week confirmed disability progression beginning at week 62 ( BID , P = 0.0454) and week 72 ( TID , P = 0.0399), compared with placebo. These effects were sustained throughout the 2‐year study period. DMF significantly reduced the odds of having a higher number of gadolinium‐enhancing lesions by 88% ( BID ) and 75% ( TID ) and the mean number of new or enlarging T2 lesions by 72% ( BID ) and 67% ( TID ), from the first post‐baseline magnetic resonance imaging assessment at 24 weeks (all P < 0.0001 versus placebo). Conclusions In phase 3 clinical trials, DMF demonstrated rapid and sustained clinical and neuroradiological efficacy in relapsing−remitting multiple sclerosis.