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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

1
Biogen Idec, Inc. Cambridge, Massachusetts.
2
Queen Square MS Centre, Institute of Neurology, University College London London, United Kingdom.
3
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada.
4
Multiple Sclerosis Program, Baylor Institute for Immunology Research Dallas, Texas.
5
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada ; NeuroRx Research Montreal, Quebec, Canada.
6
Medical University of Lodz Lodz, Poland.
7
Virginia Mason Multiple Sclerosis Center Seattle, Washington.
8
St. Vincent's University Hospital Dublin, Ireland.
9
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Cleveland, Ohio.
10
St Josef Hospital, Ruhr University Bochum, Germany.

Abstract

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.

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