Effects of delayed-release dimethyl fumarate on MRI measures in the phase 3 CONFIRM study

Neurology. 2015 Mar 17;84(11):1145-52. doi: 10.1212/WNL.0000000000001360. Epub 2015 Feb 13.

Abstract

Objective: To evaluate the effects of oral delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) on MRI lesion activity and load, atrophy, and magnetization transfer ratio (MTR) measures from the Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (CONFIRM) study.

Methods: CONFIRM was a 2-year, placebo-controlled study of the efficacy and safety of DMF 240 mg twice (BID) or 3 times daily (TID) in 1,417 patients with relapsing-remitting multiple sclerosis (RRMS); subcutaneous glatiramer acetate 20 mg once daily was included as an active reference comparator. The number and volume of T2-hyperintense, T1-hypointense, and gadolinium-enhancing (Gd+) lesions, as well as whole brain volume and MTR, were assessed in 681 patients (MRI cohort).

Results: DMF BID and TID produced significant and consistent reductions vs placebo in the number of new or enlarging T2-hyperintense lesions and new nonenhancing T1-hypointense lesions after 1 and 2 years of treatment and in the number of Gd+ lesions at week 24, year 1, and year 2. Lesion volumes were also significantly reduced. Reductions in brain atrophy and MTR changes with DMF relative to placebo did not reach statistical significance.

Conclusions: The robust effects on MRI active lesion counts and total lesion volume in patients with RRMS demonstrate the ability of DMF to exert beneficial effects on inflammatory lesion activity in multiple sclerosis, and support DMF therapy as a valuable new treatment option in RRMS.

Classification of evidence: This study provides Class I evidence of reduction in brain lesion number and volume, as assessed by MRI, over 2 years of delayed-release DMF treatment.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Delayed-Action Preparations / administration & dosage
  • Dimethyl Fumarate
  • Double-Blind Method
  • Female
  • Fumarates / administration & dosage*
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Internationality
  • Magnetic Resonance Imaging* / trends
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Treatment Outcome
  • Young Adult

Substances

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