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Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

ABSTRACT: Introduction:Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing-remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients. Objectives:The purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects. Methods:Thirty-six patients with relapsing-remitting multiple sclerosis received either dimethyl fumarate (n?=?27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n?=?9) for 12?weeks. Stool samples were collected at baseline, two and 12?weeks. We included 165 healthy individuals as controls. Results:At baseline, 16 microbial genera were altered in multiple sclerosis patients compared with healthy controls. In the dimethyl fumarate-treated patients (n?=?21) we observed a trend of reduced Actinobacteria (p?=?0.03, QFDR?=?0.24) at two weeks, mainly driven by Bifidobacterium (p?=?0.06, QFDR?=?0.69). At 12?weeks, we observed an increased abundance of Firmicutes (p?=?0.02, QFDR?=?0.09), mostly driven by Faecalibacterium (p?=?0.01, QFDR?=?0.48). Conclusions:This pilot study did not detect a major effect of dimethyl fumarate on the gut microbiota composition, but we observed a trend towards normalization of the low abundance of butyrate-producing Faecalibacterium after 12?weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.

SUBMITTER: Storm-Larsen C

PROVIDER: S-EPMC6859687 | biostudies-literature | 2019 Oct-Dec

REPOSITORIES: biostudies-literature

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Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

Storm-Larsen C C Myhr K-M KM Farbu E E Midgard R R Nyquist K K Broch L L Berg-Hansen P P Buness A A Holm K K Ueland T T Fallang L-E LE Burum-Auensen E E Hov J R JR Holmøy T T

Multiple sclerosis journal - experimental, translational and clinical 20191001 4

<h4>Introduction</h4>Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing-remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients.<h4>Objectives</h4>The purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects ...[more]

PMID: 31798939

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Project description:BackgroundDelayed-release dimethyl fumarate (DMF) has demonstrated efficacy and a favorable benefit-risk profile in phase 2 and 3 studies that enrolled predominantly white patients with relapsing-remitting multiple sclerosis (RRMS). In this study (APEX, Part I), we evaluated the efficacy/safety outcomes of DMF in a predominantly East Asian population of patients with RRMS.MethodsIn this 24-week, randomized, double-blind, placebo-controlled phase 3 study, 225 patients, 142 of which were East Asian (63.4%), were enrolled: Japan (n = 114), South Korea (n = 20), Taiwan (n = 8), the Czech Republic (n = 42), and Poland (n = 40). Key exclusion criteria included diagnosis of neuromyelitis optica spectrum disorder. Stratified by country, patients were randomized 1:1 to receive DMF 240 mg twice daily or placebo. Clinical assessments, including neurological examination and EDSS scoring, were conducted at baseline and at weeks 12 and 24.ResultsA total of 213 patients (95.1%) completed the study. From weeks 12 - 24, the total number of new gadolinium-enhancing (Gd+) lesions was reduced by 84% (p < 0.0001) in DMF compared with placebo. For the secondary endpoint, from baseline to week 24, the total number of new Gd+ lesions was reduced by 75% and the mean number of new/newly enlarging T2 hyperintense lesions was reduced by 63% (both p < 0.0001). Flushing and flushing-related symptoms, and gastrointestinal events were adverse events related to DMF treatment. Efficacy and safety results in the Japanese subgroup and the East Asian subgroup (which included patients from Japan, Taiwan, and South Korea) were consistent with the overall study population.ConclusionThe strong efficacy and favorable benefit-risk profile of DMF extends to Japanese, and more broadly, East Asian patients with RRMS.Trial registrationThis trial is registered on ClinicalTrials.gov (identifier: NCT01838668 ), April 20, 2013 (retrospectively registered). The registration can be found at the following URL: https://clinicaltrials.gov/ct2/show/NCT01838668.

Dataset Information

Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

Publications

Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial.

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