Author Of 1 Presentation
P0388 - Safety of dimethyl fumarate for multiple sclerosis: A systematic review and meta-analysis (ID 255)
Abstract
Background
The safety profile of dimethyl fumarate (DMF) used in the treatment of multiple sclerosis (MS) is not fully understood.
Objectives
The objective of this study was 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 clinicaltrials.gov 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).
Conclusions
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.