Immunomodulators and Immunosuppressants for Relapsing-Remitting Multiple Sclerosis (Rrms): a Network Meta-Analysis

Summary

A Cochrane review [Abstract] 1 included 39 studies with a total of 25 113 subjects. The majority of the included trials had a median duration of 2 years. Twenty-four (60%) were placebo-controlled and 15 (40%) were head-to-head studies.Although MRI measures are widely used in MS trials, only clinical outcomes were included in this review. The included treatments were interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine and immunoglobulins.

• Relapses: During the first 2 years of treatment, alemtuzumab, mitoxantrone, natalizumab, and fingolimod outperformed other drugs. The most effective drug was alemtuzumab (RR vs. interferon-beta 0.46, 95% CI 0.39 - 0.55; 3 studies, n=1582), followed by mitoxantrone (RR 0.47, 95% CI 0.27 to 0.81; one study, n=51), natalizumab (RR 0.56, 95% CI 0.47 to 0.66; one study, n=942), and fingolimod (RR 0.72, 95% CI 0.64 to 0.81; 2 studies, n=2355).
• Disability worsening: It was based on a surrogate marker (irreversible worsening confirmed at 3-month follow-up), measured during the first 2 years in the majority of included studies. Both direct and indirect comparisons revealed that the most effective treatments were mitoxantrone (RR vs. placebo 0.20, 95% CI 0.05 to 0.84; one study, n=51), alemtuzumab (RR 0.35, 95% CI 0.26 to 0.48; 3 studies, n=1582), and natalizumab (RR 0.64, 95% CI 0.49 to 0.85; one study, n=942).Based on the network meta-analysis methodology, the corresponding RR estimates vs. placebo over the first 2 years of follow-up were: mitoxantrone 9.92 (95% CI 0.54 to 168.84), fingolimod 1.69 (95% CI 1.32 to 2.17), natalizumab 1.53 (95% CI 0.93 to 2.53), and alemtuzumab 0.72 (95% CI 0.32 to 1.61).
• Serious adverse events (SAEs):Information was scanty, characterised by heterogeneous results and based on a very low number of events observed during the short-term duration of the trials.