What is the evidence on immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis? – A Cochrane Review summary with commentary

Abstract

Background

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system, and a leading cause of neurological disability in adults. Many drugs with different mechanisms of action and potentially serious harms are available so far, thus requiring an evidence-based decision-making for clinicians managing MS patients.

Objective

To compare the efficacy and safety of immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis (RRMS).

Methods

A systematic search was performed in CENTRAL, MEDLINE, Embase, and trials registers on 8 august 2022, including RCTs comparing immunomodulators and immunosuppressants versus placebo or another drug.

Results

The network meta-analysis (NMA) included 50 RCTs (with 36,541 participants). High-certainty evidence suggests that natalizumab largely reduces relapses at 12 (RR 0.52, 95% CI 0.43 to 0.63) and 24 months (RR 0.56, 95% CI 0.48 to 0.65), and cladribine (RR 0.53, 95% CI 0.44 to 0.64) and alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68) largely reduce relapses at 24 months. Moreover, natalizumab probably reduces disability worsening over 2 years (RR 0.59, 95% CI 0.46 to 0.75). For what concern safety, moderate-certainty evidence suggests that alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (AEs), while daclizumab, fingolimod, teriflunomide, interferon beta-1a. laquinimod, natalizumab, and glatiramer acetate probably result in a slight increase in treatment discontinuation treatment due to AEs.

Conclusions

Compared with placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. Natalizumab likely results in a large reduction of disability worsening after two years of treatment. People taking fingolimod, teriflunomide, glatiramer acetate, interferon beta-1a, laquinimod, natalizumab and daclizumab are more likely to discontinue the drug because of unwanted effects. Lack of data for treatment effects beyond two years and poor reporting of adverse events in short-term trials limit the applicability of these findings.