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

Area of Science:

• Neurology
• Immunology
• Pharmacology

Background:

• Multiple therapeutic strategies exist for relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants, and biologics.
• While therapies reduce relapse frequency, their comparative efficacy in delaying relapses or disability worsening is unclear due to limited direct comparison trials.

Purpose of the Study:

• To compare the benefit and acceptability of 15 treatments for RRMS.
• To rank these RRMS treatments based on efficacy and patient withdrawal rates due to adverse events.

Main Methods:

• Conducted a systematic search of multiple databases for randomized controlled trials (RCTs) up to September 2014.
• Included 39 RCTs with 25,113 participants, comparing 15 treatments against placebo or active agents.
• Utilized pairwise and network meta-analysis, assessing evidence quality using GRADE criteria.

Main Results:

• Alemtuzumab, mitoxantrone, natalizumab, and fingolimod showed superiority in preventing relapses within 24 months.
• Alemtuzumab demonstrated the highest efficacy (RR 0.46), followed by mitoxantrone, natalizumab, and fingolimod.
• Natalizumab was the only treatment showing a moderate-quality evidence benefit in preventing disability worsening within 24 months.

Conclusions:

• Alemtuzumab, natalizumab, and fingolimod are recommended for preventing RRMS relapses in the short term (24 months), with limited evidence for long-term benefits.
• Insufficient evidence exists to evaluate treatments for preventing irreversible disability worsening.
• Further research is needed on long-term safety, efficacy beyond two years, and direct comparisons between active agents.