Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Relapsing-remitting multiple sclerosis (RRMS) has multiple therapeutic strategies, including immunomodulators, immunosuppressants, and biological agents.
• The comparative efficacy and safety of these diverse treatments for RRMS remain unclear.
• This study updates a previous Cochrane review to provide current evidence on RRMS therapies.

Approach:

• A network meta-analysis was conducted, synthesizing data from 50 randomized controlled trials involving 36,541 participants.
• Direct and indirect evidence were considered, with placebo serving as the common comparator.
• The GRADE approach was used to assess the certainty of the evidence for various outcomes.

Key Points:

• High-certainty evidence shows natalizumab, cladribine, and alemtuzumab significantly reduce relapses at 24 months.
• Moderate-certainty evidence suggests natalizumab may slow disability worsening over 24 months.
• Most disease-modifying therapies (DMTs) are associated with increased treatment discontinuation due to adverse events, with alemtuzumab showing fewer discontinuations.

Conclusions:

• Natalizumab, cladribine, and alemtuzumab are highly effective in reducing relapses in RRMS over two years.
• Long-term efficacy and safety data beyond two years are insufficient, highlighting a need for longer follow-up studies.
• Future research should focus on direct comparisons between active agents and patient-relevant outcomes like quality of life.