Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study

Steve Vucic, Robert D. Henderson, Susan Mathers, Merrilee Needham, David Schultz, Matthew C. Kiernan, the TEALS study group, Lesley-Ann Hall, Peter Allcroft

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Objective: Neuroinflammation is an important pathogenic mechanism in amyotrophic lateral sclerosis (ALS), with regulatory T cells (Tregs) mediating a slower rate of disease progression. Dimethyl fumarate enhances Treg levels and suppresses pro-inflammatory T cells. The present study assessed the safety and efficacy of dimethyl fumarate in ALS. Methods: Phase-2, double-blind, placebo-controlled randomised clinical trial recruited participants from May 1, 2018 to September 25, 2019, across six Australian sites. Participants were randomised (2:1 ratio) to dimethyl fumarate (480 mg/day) or matching placebo, completing visits at screening, baseline, weeks 12, 24 and 36. The primary efficacy endpoint was a change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) at week 36. Secondary outcome measures included survival, neurophysiological index (NI), respiratory function, urinary neurotrophin-receptor p75 and quality of life. Results: A total of 107 participants were randomised to dimethyl fumarate (n = 72) or placebo (n = 35). ALSFRS-R score was not significantly different at week 36 (−1.12 [−3.75 to 1.52, p = 0.41]). Dimethyl fumarate was associated with a reduced NI decline week 36 (differences in the least-squares mean: (0.84 [−0.51 to 2.22, p = 0.22]). There were no significant differences in other secondary outcome measures. Safety profiles were comparable between groups. Interpretation: Dimethyl fumarate, in combination with riluzole, was safe and well-tolerated in ALS. There was no significant improvement in the primary endpoint. The trial provides class I evidence for safety and lack of efficacy of dimethyl fumarate in ALS.

Original languageEnglish
Pages (from-to)1991-1999
Number of pages9
JournalAnnals of Clinical and Translational Neurology
Issue number10
Early online date3 Sep 2021
Publication statusPublished - Oct 2021


  • Neuroinflammation
  • amyotrophic lateral sclerosis
  • ALS
  • pathogenic
  • dimethyl fumarate
  • T cells
  • Tregs


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