Efficacy of delayed-release dimethyl fumarate in early multiple sclerosis: post-hoc analysis of the phase 3 DEFINE and CONFIRM studies according to baseline disability
Author(s): ,
R. Gold
Affiliations:
St. Josef Hospital, Ruhr University, Bochum, Germany
,
G. Giovannoni
Affiliations:
Queen Mary University of London, Blizard Institute, London, United Kingdom
,
J.T. Phillips
Affiliations:
Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX
,
R.J. Fox
Affiliations:
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH
,
J.B. Lewin
Affiliations:
Biogen, Inc., Cambridge, MA, United States
,
A. Zhang
Affiliations:
Biogen, Inc., Cambridge, MA, United States
J.L. Marantz
Affiliations:
Biogen, Inc., Cambridge, MA, United States
ECTRIMS Online Library. Gold R. 10/08/15; 115562; 622
Ralf Gold
Ralf Gold
Contributions
Abstract
Abstract: P565

Type: Poster

Abstract Category: Immunomodulation / Immunosuppression

Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies. An analysis of data from the AFFIRM study of natalizumab in RRMS indicates that patients with lower levels of disability tend to demonstrate the greatest benefit on clinical outcomes (Havrdova et al, ECTRIMS 2013, P519). Hence, DMF treatment may be particularly effective in slowing disease progression and reducing overall disease burden in patients with early MS as indicated by lower levels of disability. Previous analyses of DEFINE/CONFIRM demonstrated that DMF efficacy was robust in patients newly diagnosed with MS (Gold et al. 2015) and in patients who were naïve to prior treatment with disease-modifying therapies (Hutchinson et al., ECTRIMS 2013, P563).

Objectives: Investigate the efficacy of DMF on clinical measures in RRMS patients early in their disease course according to extent of disability, defined as baseline Expanded Disability Status Scale (EDSS) score ≤2.0.

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, placebo, or subcutaneous glatiramer acetate (reference comparator; CONFIRM only) for up to 2 years. EDSS was assessed at baseline and every 12 weeks thereafter. Outcome measures included annualized relapse rate (ARR) and risk of 12-week confirmed disability progression. Results are reported for placebo and DMF BID (approved dosing regimen in all regions).

Results: The integrated intent-to-treat population included 771 and 769 patients receiving placebo or DMF BID, respectively; among them, 362 and 373 had baseline EDSS score ≤2.0. At 2 years, in patients with baseline EDSS score ≤2.0, reductions with DMF BID compared with placebo were observed for ARR (adjusted relapse rate [95% confidence interval, CI]: 0.132 [0.102, 0.170] vs 0.357 [0.291, 0.438]; 63% reduction; P< .0001) and risk of 12-week confirmed disability progression (0.14 vs 0.24; 40% reduction; P=.0066). Additional data will be reported.

Conclusions: Compared with placebo, DMF BID demonstrated beneficial effects on clinical outcomes in RRMS patients early in their disease course according to extent of disability.

Disclosure:

This study is supported by Biogen, Inc.

Ralf Gold: honoraria from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage for serving as editor of Therapeutic Advances in Neurological Disorders.

Gavin Giovannoni: honoraria from Abbvie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck Serono, Novartis, Protein Discovery Laboratories, Roche, Synthon, Teva Neuroscience, UCB, and Vertex; research grant support from Biogen, Ironwood, Merck Serono, Merz, and Novartis; compensation from Elsevier as co−chief editor of MS and Related Disorders.

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

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

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.

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

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies