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

Anna He, Tim Spelman, Vilija Jokubaitis, Eva Havrdova, Dana Horakova, Maria Trojano, Alessandra Lugaresi, Guillermo Izquierdo, Pierre Grammond, Pierre Duquette, Marc Girard, Eugenio Pucci, Gerardo Iuliano, Raed Alroughani, Celia Oreja-Guevara, Ricardo Fernandez-Bolanos, Francois Grand'Maison, Patrizia Sola, Daniele Spitaleri, Franco GranellaMurat Terzi, Jeannette Lechner-Scott, Vincent Van Pesch, Raymond Hupperts, Jose Luis Sanchez-Menoyo, Suzanne Hodgkinson, Csilla Rozsa, Freek Verheul, Helmut Butzkueven, Tomas Kalincik*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.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.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.Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy.Annualized relapse rate and proportion of relapse-free patients, as well as the proportion of patients without sustained disability progression.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.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.
Original languageEnglish
Pages (from-to)405-413
JournalJAMA Neurology
Issue number4
Publication statusPublished - Apr 2015

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