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Disease-Modifying Therapies for Relapsing–Remitting Multiple Sclerosis: A Network Meta-Analysis

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Abstract

Background

A broad range of disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) is available. However, the efficacy and safety of traditional DMTs compared with the recently developed DMTs remain unclear.

Objective

Therefore, we have synthesised available evidence of clinical outcomes for DMTs in adults with RRMS.

Methods

PubMed, Scopus and a manual search were performed. Bayesian network meta-analyses of randomised clinical trials assessing DMTs as monotherapies were conducted. SUCRA and GRADE were used to rank therapies and to assess quality of general evidence, respectively.

Results

Thirty-three studies were included in the meta-analyses. The most effective therapies for the outcome of annualised relapse rate were alemtuzumab (96% probability), natalizumab (96%) and ocrelizumab (85%), compared with all other therapies (hazard ratio versus placebo, 0.31, 0.31 and 0.37, respectively; p < 0.05 for all comparisons) (high-quality evidence). However, no significant differences among these three therapies were found. Discontinuation due to adverse events revealed similarity across all therapies, except for alemtuzumab, which showed less discontinuation when compared with interferon-1a intramuscular (relative risk 0.37; p < 0.05).

Conclusion

High-quality evidence shows that alemtuzumab, natalizumab and ocrelizumab present the highest efficacy among DMTs, and other meta-analyses are required regarding adverse events frequency, to better understand the safety of therapies. Based on efficacy profile, guidelines should consider a three-category classification (i.e. high, intermediate and low efficacy).

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Authors and Affiliations

  1. Pharmacy, Federal University of Paraná, Curitiba, Brazil

    Rosa C. Lucchetta, Fernanda S. Tonin, Helena H. L. Borba, Letícia P. Leonart, Vinicius L. Ferreira, Aline F. Bonetti, Bruno S. Riveros, Roberto Pontarolo & Astrid Wiens

  2. Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil

    Jefferson Becker

  3. Department of Social Pharmacy, Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa), University of Lisbon, Lisbon, Portugal

    Fernando Fernandez-Llimós

Authors
  1. Rosa C. Lucchetta
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  2. Fernanda S. Tonin
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Corresponding author

Correspondence to Astrid Wiens.

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Funding

This study was funded by the Institutional Development Support Program of the National Health System (Proadi-SUS) and Hospital Alemão Oswaldo Cruz (Grant number 01/2017).

Conflicts of interest

Bruno Riveros and Rosa Lucchetta report personal fees from Biogen and Roche; and Jefferson Becker reports grants and personal fees from Biogen, Novartis, Roche and Teva and personal fees from Bayer, Ipsen, Merck Serono, Sanofi, outside the submitted work. Fernanda Tonin, Helena Borba, Letícia Leonart, Vinícius Ferreira, Aline Bonetti, Roberto Pontarolo, Fernando Fernandez-Llimós and Astrid Wiens declare that they have no conflict of interest.

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Lucchetta, R.C., Tonin, F.S., Borba, H.H.L. et al. Disease-Modifying Therapies for Relapsing–Remitting Multiple Sclerosis: A Network Meta-Analysis. CNS Drugs 32, 813–826 (2018). https://doi.org/10.1007/s40263-018-0541-5

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