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


CONCLUSIONS
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.
Biogen Idec, Inc. Cambridge, Massachusetts.
Vissia
V
Viglietta
Queen Square MS Centre, Institute of Neurology, University College London London, United Kingdom.
David
D
Miller
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada.
Amit
A
Bar-Or
Multiple Sclerosis Program, Baylor Institute for Immunology Research Dallas, Texas.
J Theodore
JT
Phillips
Montreal Neurological Institute and Hospital, McGill University Montreal, Quebec, Canada ; NeuroRx Research Montreal, Quebec, Canada.
Douglas L
DL
Arnold
Medical University of Lodz Lodz, Poland.
Krzysztof
K
Selmaj
Virginia Mason Multiple Sclerosis Center Seattle, Washington.
Mariko
M
Kita
St. Vincent's University Hospital Dublin, Ireland.
Michael
M
Hutchinson
Biogen Idec, Inc. Cambridge, Massachusetts.
Minhua
M
Yang
Biogen Idec, Inc. Cambridge, Massachusetts.
Ray
R
Zhang
Biogen Idec, Inc. Cambridge, Massachusetts.
Katherine T
KT
Dawson
Biogen Idec, Inc. Cambridge, Massachusetts.
Sarah I
SI
Sheikh
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Cleveland, Ohio.
Robert J
RJ
Fox
St Josef Hospital, Ruhr University Bochum, Germany.
Ralf
R
Gold