Longer-term follow-up of the efficacy of delayed-release dimethyl fumarate in newly diagnosed patients with RRMS: an integrated analysis of DEFINE, CONFIRM, and ENDORSE
Author(s): ,
J. Marantz
Biogen, Cambridge, MA, United States
R. Gold
St. Josef Hospital, Ruhr University, Bochum, Germany
G. Giovannoni
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
J.T. Phillips
Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX
R.J. Fox
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH, United States
A. Zhang
Biogen, Cambridge, MA, United States
ECTRIMS Online Library. Marantz J. 10/08/15; 115560; 620
Jing Marantz
Jing Marantz
Abstract: P564

Type: Poster

Abstract Category: Immunomodulation / Immunosuppression

Background: Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated efficacy and safety 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.

Objective: To report long-term outcomes with DMF in newly diagnosed patients with RRMS.

Methods: In ENDORSE, patients randomised in DEFINE/CONFIRM to DMF 240 mg twice (BID) or thrice daily (TID) continued on the same dosage. Patients randomised to placebo (PBO) or glatiramer acetate (GA; CONFIRM only) were re-randomised 1:1 to DMF BID or TID. Results for DMF 240 mg BID are reported, as this represents the approved dosage. The GA arm was excluded from the parent analysis of newly diagnosed patients in DEFINE/CONFIRM. 'Newly diagnosed' was defined as multiple sclerosis diagnosis within 1 year prior to parent study entry and either treatment-naïve or previously treated with corticosteroids alone. Minimum follow-up (data as of May 14, 2014) was approximately 5 years; BID/BID patients remaining on study received approximately ≥5 years continuous DMF treatment; PBO/BID patients remaining on study received 2 years PBO (DEFINE/CONFIRM) followed by approximately ≥3 years DMF (ENDORSE).

Results: The newly diagnosed population included 144 BID/BID and 85 PBO/BID patients. At 5 years (ENDORSE Year 3), the annualised relapse rate (ARR) (95% confidence interval [CI]) in the newly diagnosed population was 0.137 (0.101, 0.186) in BID/BID and 0.169 (0.113, 0.253) in PBO/BID. Although the ARR at 5 years was lower in BID/BID patients compared with those who received delayed treatment (PBO/BID), PBO/BID patients demonstrated improvements after switching to DMF in ENDORSE: ARR (95% CI) was 0.244 (0.163, 0.367) from Years 0-2 (DEFINE/CONFIRM), and 0.102 (0.060, 0.174) from Years 3-5 (ENDORSE). The Kaplan-Meier estimated proportion (95% CI) of patients with 24-week confirmed disability progression at 5 years was 8.1% (4.6%, 14.3%) in BID/BID and 20.4% (13.0%, 31.4%) in PBO/BID. Updated 6-year data (ENDORSE Year 4) will be presented.

Conclusion: Long-term treatment with DMF demonstrated strong and sustained effects on relapses and disability progression across newly diagnosed patient subgroups (BID/BID and PBO/BID).


Supported by:

J. Marantz, A. Zhang: employees of and hold stock/stock options in Biogen.

R. Gold: consultant fees from Bayer HealthCare, Biogen, Merck Serono, Novartis, Teva Neuroscience, and Genzyme; grant/research support from Bayer HealthCare, Biogen, Genzyme, Merck Serono, Novartis, and Teva Neuroscience; compensation from Sage as editor of Therapeutic Advances in Neurological Disorders.

G. Giovannoni: honoraria from Abbvie, Bayer HealthCare, Biogen, Canbex, FivePrime, Genzyme, GlaxoSmithKline, GW Pharma, Merck, 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 Multiple Sclerosis and Related Disorders.

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

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.

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