Epub: Kappos et al. Long-term effects of fingolimod in multiple sclerosis: The randomized FREEDOMS extension trial. Neurology. 2015 Mar. pii: 10.1212/WNL.0000000000001462.
OBJECTIVE: To assess long-term safety and efficacy of fingolimod in MSers with relapsing-remitting multiple sclerosis (RRMS).
METHODS: MSers completing FTY720 Research Evaluating Effects of Daily Oral Therapy in MS (FREEDOMS) were eligible for this dose-blinded, parallel-group extension study, continuing fingolimod 0.5 mg/day or 1.25 mg/day, or switching from placebo to either dose, randomized 1:1. Efficacy variables included annualized relapse rate (ARR), brain volume loss (BVL), and confirmed disability progression (CDP). Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study. Within-group analyses compared years 0-2 (FREEDOMS) and years 2-4 (extension) in the extension ITT population.
RESULTS: Of 1,272 MSers (FREEDOMS ITT population), 1,033 were eligible, and 920 enrolled in the extension study (continuous-fingolimod: 0.5 mg [n = 331], 1.25 mg [n = 289]; placebo-fingolimod: 0.5 mg [n = 155], 1.25 mg [n = 145]); 916 formed the extension ITT population (n = 330; n = 287; n = 154; n = 145) and 773 (84%) completed. In the continuous-fingolimod groups, ARR was lower (p < 0.0001), BVL was reduced (p < 0.05), and proportionately more MSers were free from 3-month CDP (p < 0.05) than in a group comprising all placebo-fingolimod MSers. Within each placebo-fingolimod group, ARR was lower (p < 0.001, both) and BVL was reduced after switching (p < 0.01, placebo-fingolimod 0.5 mg). Rates and types of adverse events were similar across groups; no new safety issues were reported.
CONCLUSION: Efficacy benefits of fingolimod during FREEDOMS were sustained during the extension; ARR and BVL were reduced after switching.