A Cochrane review «La Mantia L, Tramacere I, Firwana B, ym. Fingolimo...»1 included 6 RCTs with a total of 5152 patients with relapsing-remitting multiple sclerosis. There were 1621 controls and 3531 treated withfingolimod at different doses; 2061 with 0.5 mg, 1376 with 1.25 mg, and 94 with 5.0 mg daily. Among the controls, 923 participants were treated with placebo and 698 with others DMDs. The treatment duration was 6 months in 3, 12 months in 1, and 24 months in 2 trials.

Whenfingolimodat the dose of 0.5 mg was compared to placebo, it increased the probability of being relapse-free at 24 months (RR 1.44, 95%CI 1.28 to 1.63; 2 trials, n=1556), but it did not prevent the disability progression (RR 1.07, 95% CI 1.02 to 1.11; 2 trials, n=1556). Benefit was observed for other measures of inflammatory disease activity, including clinical (ARR): rate ratio 0.50, 95% CI 0.40 to 0.62 (2 trials, n=1556); and magnetic resonance imaging (MRI) activity (Gd-enhancing lesions): RR of being free from (MRI) Gd-enhancing lesions: 1.36, 95% CI 1.27 to 1.45 (2 trials, n=1226). The mean change of MRI T2-weighted lesion load favouredfingolimodat 12 and 24 months. No increased risk of discontinuation due to adverse events was seen forfingolimod 0.5 mg compared to placebo at 6 and 24 months.

Comparingfingolimod0.5 mg to im. interferon beta-1a, it slightly increased the number of patients free from relapse at one year (RR 1.18, 95% CI 1.09 to 1.27; 1 trial, n=860) or from Gd-enhancing lesions (RR 1.12, 95% CI 1.05 to 1.19; 1 trial, n=860), and decreased the relapse rate (rate ratio 0.48, 95% CI 0.34 to 0.70; 1 trial, n=860). There was no effect on disability progression (RR 1.02, 95% CI 0.99 to 1.06) or significant difference for MRI T2-weighted lesion load change. It was more likely that patients discontinuedfingolimod, as compared to other DMDs, due to adverse events in the short-term (6 months) (RR 3.21, 95% CI 1.16 to 8.86), but there was no significant difference vs. interferon beta-1a at 12 months (RR 1.51, 95% CI 0.81 to 2.80). A higher incidence of adverse events was suggestive of the lower tolerability rate offingolimodcompared to interferon-beta-1a.

Comment: Trials with interferon were based on a low number of head-to-head RCTs with short follow-up duration and four studies were at high risk of bias as co-authors were affiliated with the pharmaceutical company.