Six-year follow-up of delayed-release dimethyl fumarate in RRMS: integrated clinical efficacy data from the DEFINE, CONFIRM, and ENDORSE studies
Author(s): ,
M. Hutchinson
Affiliations:
St. Vincent's University Hospital, Dublin, Ireland
,
R. Gold
Affiliations:
St. Josef Hospital, Ruhr University, Bochum, Germany
,
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, United States
,
A. Bar-Or
Affiliations:
Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada
,
L. Kappos
Affiliations:
University Hospital, Basel Neurology, Basel, Switzerland
,
R. Zhang
Affiliations:
Biogen, Cambridge, MA, United States
,
M. Yang
Affiliations:
Biogen, Cambridge, MA, United States
J. Marantz
Affiliations:
Biogen, Cambridge, MA, United States
ECTRIMS Online Library. Hutchinson M. 10/08/15; 115447; 386
Michael Hutchinson
Michael Hutchinson
Contributions
Abstract
Abstract: P543

Type: Poster

Abstract Category: Immunomodulation / Immunosuppression

Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated broad efficacy and an acceptable safety profile in patients with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 DEFINE and CONFIRM studies; ENDORSE is an 8-year extension of DEFINE/CONFIRM.

Objectives: To report long-term (6-year follow-up) clinical efficacy outcomes with DMF in patients with RRMS.

Methods: Patients randomised to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued the same dosage in ENDORSE. Patients randomised to placebo (PBO; DEFINE/CONFIRM) or glatiramer acetate (GA; CONFIRM) were re-randomised 1:1 to DMF 240 mg BID or TID. Data were analysed by treatment arm in parent/extension study: BID/BID, TID/TID, PBO/BID, PBO/TID, GA/BID, GA/TID. Results for DMF 240 mg BID are reported, as this represents the maintenance dose of DMF approved for treatment of patients with relapsing MS. At the time of the last annual data cut-off (May 14, 2014), the minimum treatment follow-up for patients continuing DMF was approximately 5 years.

Results: Of 2079 patients completing DEFINE/CONFIRM, 1736 were dosed in ENDORSE (n=501 [BID/BID], 502 [TID/TID], 249 [PBO/BID], 248 [PBO/TID], 118 [GA/BID], 118 [GA/TID]). Adjusted annualised relapse rates (ARRs) (95% confidence interval [CI]) for BID/BID during Years 1 and 2 (DEFINE/CONFIRM) and Years 3, 4, and 5 (ENDORSE) were 0.202 (0.162-0.252), 0.163 (0.128-0.208), 0.139 (0.105-0.184), 0.143 (0.109-0.188), and 0.138 (0.104- 0.183), respectively. For patients switching treatment from PBO or GA, the ARRs (95% CI) during Years 3, 4, and 5 were 0.176 (0.121-0.255), 0.131 (0.086-0.198), and 0.107 (0.068- 0.171) for PBO/BID and 0.182 (0.109-0.302), 0.137 (0.077-0.245), and 0.118 (0.062-0.225) for GA/BID, respectively. Estimated probability of disability progression remained low among patients continuing DMF. Updated data (6-year follow-up) will be presented.

Conclusions: Treatment with DMF was associated with low relapse rates and estimated probability of disability progression over 5 years; these results support its use as a long-term treatment option for patients with RRMS.

Disclosure: Supported by: Biogen.

M. Hutchinson: honoraria from Bayer Schering, Biogen, Merck-Serono, and Novartis; editorial fees from the Multiple Sclerosis Journal.

R. 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.

R.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.

J.T. Phillips: Consultant fees from Acorda, Biogen, Genzyme, Merck, Novartis, Sanofi, Teva, and XenoPort; research support from Roche.

A. Bar-Or: Honoraria/research support from Biogen, DioGenix, Genentech, GlaxoSmithKline, Guthy-Jackson Charitable Foundation, Medimmune, Merck Serono, Novartis, Ono Pharmacia, Receptos, Roche, Sanofi-Aventis, and Teva Neuroscience.

L. Kappos: Steering committee/advisory board/consultant fees for Actelion, Addex, Bayer Health Care, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi-Aventis, Santhera, Siemens, Teva, UCB, Xenoport; speaker fees for Bayer Health Care, Biogen, Merck, Novartis, Sanofi-Aventis, Teva; educational support from Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva; royalties from Neurostatus Systems GmbH; grants from Bayer HealthCare, Biogen, Merck, Novartis, Roche, Swiss MS Society, Swiss National Research Foundation, European Union, Roche Research Foundations.

R. Zhang, M. Yang, J. Marantz: Employees of and hold stock/stock options in Biogen.

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