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Ann Clin Transl Neurol. 2015 Feb;2(2):103-18. doi: 10.1002/acn3.148. Epub 2014 Dec 4.

Efficacy of delayed-release dimethyl fumarate in relapsing-remitting multiple sclerosis: integrated analysis of the phase 3 trials.

Author information

Biogen Idec, Inc. Cambridge, Massachusetts.
Queen Square MS Centre, Institute of Neurology, University College London London, United Kingdom.
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada.
Multiple Sclerosis Program, Baylor Institute for Immunology Research Dallas, Texas.
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada ; NeuroRx Research Montreal, Quebec, Canada.
Medical University of Lodz Lodz, Poland.
Virginia Mason Multiple Sclerosis Center Seattle, Washington.
St. Vincent's University Hospital Dublin, Ireland.
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Cleveland, Ohio.
St Josef Hospital, Ruhr University Bochum, Germany.



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.


A prespecified integrated analysis of the randomized, double-blind, placebo-controlled, Phase 3 DEFINE and CONFIRM trials was conducted.


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.


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.

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