PT - JOURNAL ARTICLE AU - Ludwig Kappos AU - Paul O'Connor AU - Ernst-Wilhelm Radue AU - Chris Polman AU - Reinhard Hohlfeld AU - Krzysztof Selmaj AU - Shannon Ritter AU - Rolf Schlosshauer AU - Philipp von Rosenstiel AU - Lixin Zhang-Auberson AU - Gordon Francis TI - Long-term effects of fingolimod in multiple sclerosis AID - 10.1212/WNL.0000000000001462 DP - 2015 Apr 14 TA - Neurology PG - 1582--1591 VI - 84 IP - 15 4099 - http://n.neurology.org/content/84/15/1582.short 4100 - http://n.neurology.org/content/84/15/1582.full SO - Neurology2015 Apr 14; 84 AB - Objective: To assess long-term safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS).Methods: Patients 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 patients (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 patients were free from 3-month CDP (p < 0.05) than in a group comprising all placebo–fingolimod patients. 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.Classification of evidence: This study provides Class IV evidence that long-term fingolimod treatment is well-tolerated and reduces relapse rates, disability progression, and MRI effects in patients with RRMS.AE=adverse event; ARR=annualized relapse rate; BVL=brain volume loss; CI=confidence interval; EDSS=Expanded Disability Status Scale; EoS=end of study; FREEDOMS=FTY720 Research Evaluating Effects of Daily Oral Therapy in MS; Gd=gadolinium; HR=hazard ratio; ITT=intent-to-treat; MS=multiple sclerosis; RRMS=relapsing-remitting multiple sclerosis; TRANSFORMS=Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting MS