Comparison of Switch to Fingolimod or Interferon Beta/Glatiramer Acetate in Active Multiple Sclerosis

Havrdova, Eva Kubala/0000-0002-9543-4359; Horakova, Dana/0000-0003-1915-0036; Lugaresi, Alessandra/0000-0003-2902-5589; amato, Maria Pia/0000-0003-3325-3760; pietrolongo, erika/0000-0002-6311-5994; Shaygannejad, Vahid/0000-0002-6226-0161; McCombe, Pamela/0000-0003-2704-8517; Jokubaitis, Vilija G./0000-0002-3942-4340; Oreja-Guevara, Celia/0000-0002-9221-5716; pucci, eugenio/0000-0001-7606-7330; Sanchez Menoyo, Jose Luis/0000-0003-2634-8294; Trojano, Maria/0000-0002-6329-8946; Shaygannejad, Vahid/0000-0002-9732-4153; Skibina, Olga/0000-0002-6275-8138; Vucic, Steve/0000-0002-8323-873X; Kalincik, Tomas/0000-0003-3778-1376; Sirbu, Carmen Adella/0000-0002-1982-1066; van Pesch, Vincent/0000-0003-2885-9004; Slee, Mark/0000-0003-4323-2453; Butzkueven, Helmut/0000-0003-3940-8727; Hodgkinson, Suzanne/0000-0002-9029-6663; Petersen, Thor/0000-0001-5633-2600 WOS: 000354353900008 PubMed: 25665031 IMPORTANCE After multiple sclerosis (MS) relapse while a patient is receiving an injectable disease-modifying drug, many physicians advocate therapy switch, but the relative effectiveness of different switch decisions is often uncertain. OBJECTIVE To compare the effect of the oral immunomodulator fingolimod with that of all injectable immunomodulators (interferons or glatiramer acetate) on relapse rate, disability, and treatment persistence in patients with active MS. DESIGN, SETTING, AND PARTICIPANTS Matched retrospective analysis of data collected prospectively from MSBase, an international, observational cohort study. The MSBase cohort represents a population of patients with MS monitored at large MS centers. The analyzed data were collected between July 1996 and April 2014. Participants included patients with relapsing-remitting MS who were switching therapy to fingolimod or injectable immunomodulators up to 12 months after on-treatment clinical disease activity (relapse or progression of disability), matched on demographic and clinical variables. Median follow-up duration was 13.1 months (range, 3-80). Indication and attrition bias were controlled with propensity score matching and pairwise censoring, respectively. Head-to-head analyses of relapse and disability outcomes used paired, weighted, negative binomial models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity analyses were conducted. EXPOSURES Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy. MAIN OUTCOMES AND MEASURES Annualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression. RESULTS Overall, 379 patients in the injectable group were matched to 148 patients in the fingolimod group. The fingolimod group had a lower mean annualized relapse rate (0.31 vs 0.42; 95% CI, 0.02-0.19; P = .009), lower hazard of first on-treatment relapse (hazard ratio [HR], 0.74; 95% CI, 0.56-0.98; P = .04), lower hazard of disability progression (HR, 0.53; 95% CI, 0.31-0.91; P = .02), higher rate of disability regression (HR, 2.0; 95% CI, 1.2-3.3; P = .005), and lower hazard of treatment discontinuation (HR, 0.55; P = .04) compared with the injectable group. CONCLUSIONS AND RELEVANCE Switching from injectable immunomodulators to fingolimod is associated with fewer relapses, more favorable disability outcomes, and greater treatment persistence compared with switching to another injectable preparation following on-treatment activity of MS. Novartis Pharma; Multiple Sclerosis Research Australia [11-054]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [628856, 1071124, 1032484]; Centre For Research Excellence grant [1001216]; MSBase Foundation; Biogen IdecBiogen; Sanofi; Merck SeronoMerck SeronoMerck & Company; Bayer ScheringBayer AG This investigator-initiated analysis was financially supported by Novartis Pharma, Multiple Sclerosis Research Australia (fellowship 11-054), National Health and Medical Research Council (fellowships 628856 and 1071124, grant 1032484, and Centre For Research Excellence grant 1001216), and MSBase Foundation (a not-for-profit organization that receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis Pharma, and Sanofi).