Comparative efficacy and acceptability of disease-modifying therapies in patients with relapsing-remitting multiple sclerosis: a systematic review and network meta-analysis.

Abstract

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. 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 24months) and acceptability (treatment discontinuation due to adverse events over 24months). We identified 23 suitable trials encompassing 14,096 participants. During the 2years 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 14mg, 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 7mg, 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 14mg) for the number of participants with serious adverse events. All DMTs were superior to placebo in reducing the relapse rate during the 2years 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.