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

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, Heze Municipal Hospital, Shandong, China

    Huihui Li, Fengli Hu, Yanli Zhang & Kai Li

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  1. Huihui Li
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Contributions

HHL, FLH, YLZ and KL conceived and designed the study. HHL and FLH selected the articles and extracted the data. YLZ and KL analysed the data. HHL and FLH wrote the first draft of the manuscript. YLZ and KL interpreted the data and wrote the final version. All authors read and met the ICMJE criteria for authorship and agree with the results and conclusions of this Article.

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Correspondence to Yanli Zhang.

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On behalf of all authors, the corresponding author states that there is no conflict of interest.

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Not applicable. The manuscript does not contain clinical studies or patient data.

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Li, H., Hu, F., Zhang, Y. et al. Comparative efficacy and acceptability of disease-modifying therapies in patients with relapsing–remitting multiple sclerosis: a systematic review and network meta-analysis. J Neurol 267, 3489–3498 (2020). https://doi.org/10.1007/s00415-019-09395-w

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