Comparative Efficacy and Acceptability of Disease-Modifying Therapies in Patients with Relapsing-Remitting Multiple Sclerosis: A Systematic Review and Network Meta-Analysis

BACKGROUND: Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). The treatment of MS has always been a focus of neurological research. To date, the US Food and Drug Administration (FDA) 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 (WHO) International Clinical Trials Registry Platform for RCTs published up to Jan 31, 2018. The primary outcome was efficacy (relapse rate over 24 months) and acceptability (treatment discontinuation due to adverse events over 24 months). This study is registered with PROSPERO (CRD 42018080889). 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. Funding: No specific funding was received for this work. Declaration of Interest: JZ, YLZ, JT, JLL, JFL, JFZ, DYK, JYL, YJM, RHH and SLS declare no competing interests.