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

Area of Science:

• Neurology and Immunology
• Clinical Trial Analysis
• Pharmacological Research

Background:

• Emerging immunomodulatory and immunosuppressive treatments for progressive multiple sclerosis (PMS) offer new options.
• Lack of direct comparison trials hinders understanding of relative benefits and safety profiles for PMS treatments.

Purpose of the Study:

• To conduct a network meta-analysis comparing the efficacy and safety of numerous treatments for progressive multiple sclerosis (PMS).
• To evaluate treatments including alemtuzumab, fingolimod, natalizumab, ocrelizumab, rituximab, and interferon beta for PMS.

Main Methods:

• Systematic search of CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP up to August 2022.
• Inclusion of 23 randomized controlled trials (RCTs) with 10,167 participants comparing monotherapy to placebo or active agents.
• Data synthesis using pair-wise and network meta-analysis, with evidence certainty assessed by GRADE.

Main Results:

• Moderate certainty evidence suggests rituximab may slightly reduce relapses over 24 months and interferon beta-1b over 36 months compared to placebo.
• High certainty evidence indicates interferon beta-1a increases discontinuation due to adverse events; moderate certainty suggests similar increases for rituximab, interferon beta-1b, immunoglobulins, glatiramer acetate, fingolimod, and ocrelizumab.
• Low to very low certainty evidence was found for disability progression and serious adverse events, often due to imprecision and short follow-up.

Conclusions:

• Rituximab and interferon beta-1b may offer slight relapse reduction in progressive multiple sclerosis (PMS), but with increased adverse event discontinuation rates.
• Limited certainty of evidence for disability progression and serious adverse events necessitates further research.
• Future research should prioritize head-to-head trials with longer follow-up periods and consistent outcome measures meaningful to patients.