Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS)

Mult Scler. 2015 Jan;21(1):57-66. doi: 10.1177/1352458514537013. Epub 2014 Jul 2.

Abstract

Background: Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in the Phase 3 DEFINE and CONFIRM trials.

Objective: To evaluate delayed-release DMF in newly diagnosed relapsing-remitting multiple sclerosis (RRMS) patients, in a post-hoc analysis of integrated data from DEFINE and CONFIRM.

Methods: Patients included in the analysis were diagnosed with RRMS within 1 year prior to study entry and naive to MS disease-modifying therapy.

Results: The newly diagnosed population comprised 678 patients treated with placebo (n = 223) or delayed-release DMF 240 mg BID (n = 221) or TID (n = 234). At 2 years, delayed-release DMF BID and TID reduced the annualized relapse rate by 56% and 60% (both p < 0.0001), risk of relapse by 54% and 57% (both p < 0.0001), and risk of 12-week confirmed disability progression by 71% (p < 0.0001) and 47% (p = 0.0085) versus placebo. In a subset of patients (MRI cohort), delayed-release DMF BID and TID reduced the mean number of new or enlarging T2-hyperintense lesions by 80% and 81%, gadolinium-enhancing lesion activity by 92% and 92%, and mean number of new non-enhancing T1-hypointense lesions by 68% and 70% (all p < 0.0001 versus placebo). Flushing and gastrointestinal events were associated with delayed-release DMF.

Conclusion: Delayed-release DMF improved clinical and neuroradiological outcomes relative to placebo in newly diagnosed RRMS patients.

Keywords: Delayed-release dimethyl fumarate; efficacy; multiple sclerosis; newly diagnosed; safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Clinical Trials, Phase III as Topic
  • Delayed-Action Preparations
  • Dimethyl Fumarate
  • Female
  • Fumarates / administration & dosage
  • Fumarates / adverse effects
  • Fumarates / pharmacology*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacology*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Treatment Outcome

Substances

  • Delayed-Action Preparations
  • Fumarates
  • Immunosuppressive Agents
  • Dimethyl Fumarate