Efficacy of delayed-release dimethyl fumarate vs glatiramer acetate on a novel composite outcome measure of inflammatory disease activity: post-hoc analysis of the CONFIRM study
Author(s): ,
M. Kremenchutzky
Affiliations:
London Health Sciences Centre, London, ON, Canada
,
R.J. Fox
Affiliations:
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH
,
J.T. Phillips
Affiliations:
Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX
,
M. Kita
Affiliations:
Virginia Mason Multiple Sclerosis Center, Seattle, WA
,
K.E. Peace
Affiliations:
Jiann-Pingg Hsu College of Public Health, Georgia Southern University, Statesboro, GA; Department of Biostatistics, School of Medicine, Virginia Commonwealth University, Richmond, VA
,
J.B. Lewin
Affiliations:
Biogen, Inc., Cambridge, MA, United States
,
A. Zhang
Affiliations:
Biogen, Inc., Cambridge, MA, United States
,
M. Okwuokenye
Affiliations:
Biogen, Inc., Cambridge, MA, United States
,
M.R. Edwards
Affiliations:
Biogen, Inc., Cambridge, MA, United States
J.L. Marantz
Affiliations:
Biogen, Inc., Cambridge, MA, United States
ECTRIMS Online Library. Kremenchutzky M. 10/09/15; 116024; 1572
Marcelo Kremenchutzky
Marcelo Kremenchutzky
Contributions
Abstract
Abstract: P1063

Type: Poster

Abstract Category: Immunomodulation / Immunosuppression

Background: Compared with placebo (PBO), delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE/CONFIRM studies. To more fully examine the effect of DMF on active inflammatory MS, we developed a novel composite endpoint combining relapse, gadolinium-enhancing (Gd+) lesions, and new/enlarging T2 lesions.

Objectives: Compare the efficacy of DMF vs glatiramer acetate (GA) on inflammatory disease activity in a post-hoc analysis of the CONFIRM study.

Methods: Eligibility criteria included age 18-55 years and EDSS score 0-5.0. Patients were randomized to receive DMF 240 mg twice (BID) or thrice daily, PBO, or subcutaneous GA (reference comparator) for up to 2 years (96 weeks). Brain MRI scans were performed in a subset of patients (MRI cohort). Inflammatory disease activity was defined as an event (relapse, Gd+ lesion, or new/enlarging T2 lesion) occurring within a specified interval (week 0−24, 24−48, or 48−96). Patients were considered free of inflammatory disease activity if they did not experience an event within a given interval or any preceding intervals, and were evaluated for inflammatory disease activity as long as they were known to be at risk. Estimate of an underlying proportional hazards model in continuous time was based on a complementary log-log model adjusted for baseline number of relapses (≤1 vs ≥2), EDSS score (≤2.0 vs >2.0), presence or absence of Gd+ lesions, and T2 lesion volume (≤median vs >median). Results are reported for DMF BID (approved dosing regimen in all regions).

Results: The intent-to-treat population included 359, 350, and 363 patients receiving DMF, GA, or PBO, respectively; among them, 169, 175, and 167 were in the MRI cohort. Life-table estimates of the proportion (standard error) of patients receiving DMF vs GA who were free of inflammatory disease activity were 36% (4%) vs 29% (3%) during week 0−24, 34% (4%) vs 23% (3%) during week 24−48, and 21% (3%) vs 16% (3%) during week 48−96. The overall hazard ratio (HR) (95% confidence interval [CI]) for DMF vs GA was 0.77 (0.59−0.99; P=.0446). To confirm the efficacy of DMF on this novel endpoint, we also compared the effects of DMF vs PBO: the overall HR (95% CI) for DMF vs PBO was 0.60 (0.46−0.79; P=.0002).

Conclusions: DMF significantly reduced the risk of inflammatory disease activity over 2 years compared with GA. The differential treatment effect was seen by 24 weeks.

Disclosure: This study is supported by Biogen, Inc.

Marcelo Kremenchutzky: Research support/consulting fees from Biogen, Sanofi, Genzyme, Novartis, Bayer, Teva, and Serono.

Robert J. Fox: consultant fees from Biogen, MedDay, Novartis, Questcor, Teva, and Xenoport; served on advisory committees for Biogen, and Novartis; research grant funding from Novartis.

J. Theodore Phillips: consulting fees from Acorda, Biogen, Genzyme, Merck Serono, and Sanofi; research support from Roche.

Mariko Kita: served as PI on studies sponsored by Biogen, Novartis, Acorda and Serono; on the speaker´s bureau for Biogen; participated in advisory boards for Biogen and Novartis; honoraria and fees were paid directly to her employer and personal compensation was limited to travel/lodging reimbursement.

Karl E. Peace: Biostatistical Consultant to Biogen.

James B. Lewin: employee of and holds stock/stock options in Biogen, Inc.

Annie Zhang: employee of and holds stock/stock options in Biogen, Inc.

Macaulay Okwuokenye: employee of and holds stock/stock options in Biogen, Inc.

Michael R. Edwards: employee of and holds stock/stock options in Biogen, Inc.

Jing L. Marantz: employee of and holds stock/stock options in Biogen, Inc.

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