Safety of dimethyl fumarate for multiple sclerosis: A systematic review and meta-analysis

Geoffrey Liang, Julia Chai, Huah Shin Ng, Helen Tremlett

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)


Background: The safety profile of dimethyl fumarate (DMF) for multiple sclerosis (MS) is not fully understood. Objective: To systematically review the literature for adverse events (AE) associated with DMF for MS. Methods: We searched MEDLINE, EMBASE, CINAHL, Web of Science, CENTRAL, and for articles published from database inception to May/2019. Studies (observational and randomized controlled trials (RCTs)) reporting AEs, serious AEs (SAE), or discontinuation due to AEs were included. We summarized the proportion of DMF-exposed patients affected and calculated the risk ratios (RR) and number needed to treat for an additional harmful outcome (NNTH) and 95% confidence intervals (CI) for the DMF relative to placebo-exposed participants. RCT findings were pooled via meta-analyses. Results: Twenty-one observational studies, 4 RCTs, 1 RCT extension study, and 2 open-label studies were included, totalling 12,380 MS patients on DMF followed for an average of 19.8 months. Compared to placebo, DMF-exposed patients had a higher risk of grade III/IV lymphopenia (NNTH = 28.8;95%CI:20.2–50.5), pruritus (NNTH = 22.1;95%CI:14.0–52.3), flushing (NNTH = 3.7;95%CI:3.3–4.1), gastrointestinal related events (NNTH = 5.7;95%CI:3.5–15.7), nausea (NNTH = 23.4;95%CI:14.9–54.7), diarrhea (NNTH = 21.2;95%CI:13.6–47.6), and abdominal pain (NNTH = 19.2;95%CI:12.9–37.9). Patients discontinued DMF because of GI symptoms (498/5619;8.9%), lymphopenia (163/4003;4.1%), and flushing (173/4779;3.6%). From pooled analyses of 4 RCTs, AE risks were higher in the DMF versus placebo groups (RR = 1.37;95%CI:1.27–1.48), but SAEs were similar (RR = 1.01;95%CI:0.77–1.33). Conclusion: Over the short-term, DMF was associated with a higher risk of AEs. The NNTH included 4 for flushing, 6 for gastrointestinal complaints, and 29 for severe or life-threatening (grade III/IV) lymphopenia. The longer-term safety of DMF, including consequences of lymphopenia remain unknown.

Original languageEnglish
Article number102566
Number of pages14
JournalMultiple Sclerosis and Related Disorders
Publication statusPublished - Nov 2020
Externally publishedYes


  • Adverse events
  • Dimethyl fumarate
  • Meta-analysis
  • Multiple sclerosis
  • Safety
  • Systematic review


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