Background: Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system. The treatment of MS has always been a focus of neurological research. To date, the US Food and Drug Administration has approved 15 medications for modifying the course of multiple sclerosis. In this study, we examined the effects of disease-modifying therapies (DMTs) on clinical outcomes.
Methods: We did a systematic review and network meta-analysis based on randomized controlled trials (RCTs) comparing DMTs in patients with relapsing-remitting multiple sclerosis (RRMS). We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for RCTs published up to Oct 31, 2018. The primary outcome was efficacy (relapse rate over 24 months) and acceptability (treatment discontinuation due to adverse events over 24 months).
Findings: We identified 23 suitable trials encompassing 14,096 participants. During the 2 years of follow-up, all drugs were significantly more effective than were placebos. The risk ratios with 95% credible intervals were as follows: alemtuzumab, 0.49 (0.40, 0.59); ocrelizumab, 0.49 (0.40, 0.61); mitoxantrone, 0.47 (0.27, 0.80); natalizumab, 0.51 (0.43, 0.61); fingolimod, 0.57 (0.50, 0.65); peginterferon beta-1a, 0.63 (0.52, 0.77); dimethyl fumarate, 0.65 (0.56, 0.74); teriflunomide 14 mg, 0.78 (0.66, 0.92); glatiramer acetate, 0.80 (0.72, 0.89); IFN β-1a (Rebif), 0.81 (0.72, 0.90); IFN β-1b (Betaseron), 0.81 (0.72, 0.91); teriflunomide 7 mg, 0.83 (0.71, 0.98); and IFN β-1a (Avonex). 0.87 (0.77, 0.99). Risk ratios compared with placebo for discontinuation due to adverse events ranged from 1.12 for the best drug (fingolimod) to 0.10 for the worst drug (mitoxantrone); from 0.24 (alemtuzumab) to 0.89 (IFNβ-1b [Betaseron]) for sustained (3-month) disability progression; and from 0.85 (natalizumab) to 1.25 (teriflunomide 14 mg) for the number of participants with serious adverse events.
Interpretation: All DMTs were superior to placebo in reducing the relapse rate during the 2 years of follow-up. As to the comparison between drugs, alemtuzumab, ocrelizumab, natalizumab and fingolimod had a relatively higher response and lower dropout rates than did the other DMTs.
Keywords: Disease-modifying therapy; Network meta-analysis; Relapsing–remitting multiple sclerosis; Systematic review.
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.Cochrane Database Syst Rev. 2013 Jun 6;(6):CD008933. doi: 10.1002/14651858.CD008933.pub2. Cochrane Database Syst Rev. 2013. PMID: 23744561 Review.
Teriflunomide for multiple sclerosis.Cochrane Database Syst Rev. 2016 Mar 22;3:CD009882. doi: 10.1002/14651858.CD009882.pub3. Cochrane Database Syst Rev. 2016. PMID: 27003123 Review.
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.Cochrane Database Syst Rev. 2015 Sep 18;(9):CD011381. doi: 10.1002/14651858.CD011381.pub2. Cochrane Database Syst Rev. 2015. PMID: 26384035 Review.
Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.Cochrane Database Syst Rev. 2017 Apr 25;4(4):CD012200. doi: 10.1002/14651858.CD012200.pub2. Cochrane Database Syst Rev. 2017. PMID: 28440858 Free PMC article. Review.
Comparative efficacy of disease-modifying therapies for patients with relapsing remitting multiple sclerosis: Systematic review and network meta-analysis.Mult Scler Relat Disord. 2016 Sep;9:23-30. doi: 10.1016/j.msard.2016.06.001. Epub 2016 Jun 8. Mult Scler Relat Disord. 2016. PMID: 27645339 Review.
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