Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study

Mult Scler. 2017 Feb;23(2):253-265. doi: 10.1177/1352458516649037. Epub 2016 Jul 11.

Abstract

Background: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM.

Objective: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE).

Methods: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID.

Results: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia.

Conclusion: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF.

Keywords: DEFINE; ENDORSE; Expanded Disability Status Scale; Relapsing–remitting multiple sclerosis; delayed-release dimethyl fumarate (DMF).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Dimethyl Fumarate / therapeutic use*
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Magnetic Resonance Imaging / methods
  • Male
  • Multiple Sclerosis / drug therapy*
  • Time Factors
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Glatiramer Acetate
  • Dimethyl Fumarate