Open AccessEfficacy of delayed‐release dimethyl fumarate in relapsing‐remitting multiple sclerosis: integrated analysis of the phase 3 trials
Author(s) -
Viglietta Vissia,
Miller David,
BarOr Amit,
Phillips J. Theodore,
Arnold Douglas L.,
Selmaj Krzysztof,
Kita Mariko,
Hutchinson Michael,
Yang Minhua,
Zhang Ray,
Dawson Katherine T.,
Sheikh Sarah I.,
Fox Robert J.,
Gold Ralf
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.148
Subject(s) - medicine , dimethyl fumarate , placebo , multiple sclerosis , cohort , population , gastroenterology , clinical trial , phases of clinical research , surgery , pathology , immunology , alternative medicine , environmental health
Objective Obtain a more precise estimate of the efficacy of delayed‐release dimethyl fumarate ( DMF ; also known as gastro‐resistant DMF ) in relapsing multiple sclerosis ( MS ) and examine the consistency of DMF 's effects across patient subgroups stratified by baseline demographic and disease characteristics. Methods A prespecified integrated analysis of the randomized, double‐blind, placebo‐controlled, Phase 3 DEFINE and CONFIRM trials was conducted. Results The intent‐to‐treat population comprised 2301 patients randomized to receive placebo ( n = 771) or DMF 240 mg twice daily ( BID ; n = 769) or three times daily ( TID ; n = 761). At 2 years, DMF BID and TID reduced the annualized relapse rate by 49% and 49% (both P < 0.0001), risk of relapse by 43% and 47% (both P < 0.0001), risk of 12‐week confirmed disability progression by 32% ( P = 0.0034) and 30% ( P = 0.0059), and risk of 24‐week confirmed disability progression by 29% ( P = 0.0278) and 32% ( P = 0.0177), respectively, compared with placebo. In a subset of patients ( MRI cohort), DMF BID and TID reduced the mean number of new/enlarging T2‐hyperintense lesions by 78% and 73%, gadolinium‐enhancing lesion activity by 83% and 70%, and mean number of new nonenhancing T1‐hypointense lesions by 65% and 64% (all P < 0.0001 vs. placebo). Effects were generally consistent across patient subgroups. Interpretation The integrated analysis provides a more precise estimate of DMF 's efficacy. DMF demonstrated a robust reduction in disease activity and a consistent therapeutic effect across patient subgroups.