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.

Department of Basic Medical Sciences Neuroscience and Sense Organs University of Bari Bari Italy

Department of Medicine John Hunter Hospital Newcastle Australia21Hunter Medical Research Institute University of Newcastle Newcastle Australia

Department of Medicine University of Melbourne Melbourne Australia

Department of Nephrology Liverpool Hospital Liverpool Australia26Department of Neurology Liverpool Hospital Liverpool Australia

Department of Neurology Amiri Hospital Kuwait City Kuwait

Department of Neurology and Center of Clinical Neuroscience General University Hospital Prague Czech Republic4Department of Neurology and Center for Clinical Neuroscience Charles University Prague Czech Republic

Department of Neurology Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Italy

Department of Neurology Cliniques Universitaires Saint Luc Brussels Belgium

Department of Neurology Hôpital Notre Dame Montreal Quebec Canada

Department of Neurology Hospital de Galdakao Usansolo Galdakao Spain

Department of Neurology Hospital Universitario Virgen de Valme Seville Spain

Department of Neurology Hospital Universitario Virgen Macarena Sevilla Spain

Department of Neurology Hotel Dieu de Lévis Lévis Quebec Canada

Department of Neurology Jahn Ferenc Teaching Hospital Budapest Hungary

Department of Neurology Nuovo Ospedale Civile San Agostino Modena Italy

Department of Neurology Orbis Medical Center Sittard the Netherlands

Department of Neurology Ospedali Riuniti di Salerno Salerno Italy

Department of Neurology Royal Melbourne Hospital Melbourne Australia

Department of Neurology Royal Melbourne Hospital Melbourne Australia2Department of Medicine University of Melbourne Melbourne Australia

Department of Neurology Royal Melbourne Hospital Melbourne Australia2Department of Medicine University of Melbourne Melbourne Australia29Department of Neurology Box Hill Hospital Monash University Melbourne Australia

Institute of Neurology University of Parma Parma Italy

Medical Faculty Department of Neurology Ondokuz Mayis University Samsun Turkey

MS Center Department of Neuroscience Imaging and Clinical Sciences University G d'Annunzio Chienti Italy

Multiple Sclerosis Unit University Hospital San Carlos Madrid Spain

Neuro Rive Sud Hôpital Charles LeMoyne Quebec City Quebec Canada

Neurology Unit Azienda Sanitaria Unica Regionale Marche Macerata Italy

Neurology Unit Groen Hart Ziekenhuis Gouda the Netherlands

Komentář v

JAMA Neurol. 2015 Apr;72(4):387-9. doi: 10.1001/jamaneurol.2014.4494. PubMed

Komentář v

Nat Rev Neurol. 2015 Jun;11(6):316-7. doi: 10.1038/nrneurol.2015.59. PubMed

Erratum v

JAMA Neurol. 2015 Aug;72(8):950. doi: 10.1001/jamaneurol.2015.1752. PubMed

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