Journal article
Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study
Annals of Clinical and Translational Neurology, Vol.8(10), pp.1991-1999
2021
Abstract
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.
Details
- Title
- Safety and efficacy of dimethyl fumarate in ALS: randomised controlled study
- Authors/Creators
- S. Vucic (Author/Creator) - Concord Repatriation General HospitalR.D. Henderson (Author/Creator) - Royal Brisbane and Women's HospitalS. Mathers (Author/Creator) - Calvary Health Care BethlehemM. Needham (Author/Creator) - Fiona Stanley HospitalD. Schultz (Author/Creator) - Flinders Medical CentreM.C. Kiernan (Author/Creator) - The University of Sydney
- Publication Details
- Annals of Clinical and Translational Neurology, Vol.8(10), pp.1991-1999
- Publisher
- Wiley Periodicals, Inc on behalf of American Neurological Association
- Identifiers
- 991005540968107891
- Copyright
- © 2021 The Authors.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.52 Neurodegenerative Diseases
- 1.52.765 ALS Mechanisms
- Web Of Science research areas
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior