title: Comparison of switch to fingolimod or interferon beta/glatiramer acetate in active multiple sclerosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  Patients had received fingolimod, interferon beta, or glatiramer acetate for a minimum of 3 months following a switch of immunomodulatory therapy.
  
  
  METHODS
  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
  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.
authors: Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.
authors: Anna
authors: A
authors: He
authors: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Tim
authors: T
authors: Spelman
authors: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Vilija
authors: V
authors: Jokubaitis
authors: 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.
authors: Eva
authors: E
authors: Havrdova
authors: 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.
authors: Dana
authors: D
authors: Horakova
authors: Department of Basic Medical Sciences, Neuroscience, and Sense Organs, University of Bari, Bari, Italy.
authors: Maria
authors: M
authors: Trojano
authors: MS Center, Department of Neuroscience, Imaging, and Clinical Sciences, University G. d'Annunzio, Chienti, Italy.
authors: Alessandra
authors: A
authors: Lugaresi
authors: Department of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors: Guillermo
authors: G
authors: Izquierdo
authors: Department of Neurology, Hotel-Dieu de Lévis, Lévis, Quebec, Canada.
authors: Pierre
authors: P
authors: Grammond
authors: Department of Neurology, Hôpital Notre Dame, Montreal, Quebec, Canada.
authors: Pierre
authors: P
authors: Duquette
authors: Department of Neurology, Hôpital Notre Dame, Montreal, Quebec, Canada.
authors: Marc
authors: M
authors: Girard
authors: Neurology Unit, Azienda Sanitaria Unica Regionale Marche, Macerata, Italy.
authors: Eugenio
authors: E
authors: Pucci
authors: Department of Neurology, Ospedali Riuniti di Salerno, Salerno, Italy.
authors: Gerardo
authors: G
authors: Iuliano
authors: Department of Neurology, Amiri Hospital, Kuwait City, Kuwait.
authors: Raed
authors: R
authors: Alroughani
authors: Multiple Sclerosis Unit, University Hospital San Carlos, Madrid, Spain.
authors: Celia
authors: C
authors: Oreja-Guevara
authors: Department of Neurology, Hospital Universitario Virgen de Valme, Seville, Spain.
authors: Ricardo
authors: R
authors: Fernandez-Bolaños
authors: Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec City, Quebec, Canada.
authors: Francois
authors: F
authors: Grand'Maison
authors: Department of Neurology, Nuovo Ospedale Civile San Agostino, Modena, Italy.
authors: Patrizia
authors: P
authors: Sola
authors: Department of Neurology, Azienda Ospedaliera di Rilievo Nazionale, San Giuseppe Moscati, Avellino, Italy.
authors: Daniele
authors: D
authors: Spitaleri
authors: Institute of Neurology, University of Parma, Parma, Italy.
authors: Franco
authors: F
authors: Granella
authors: Medical Faculty, Department of Neurology, Ondokuz Mayis University, Samsun, Turkey.
authors: Murat
authors: M
authors: Terzi
authors: Department of Medicine, John Hunter Hospital, Newcastle, Australia21Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia.
authors: Jeannette
authors: J
authors: Lechner-Scott
authors: Department of Neurology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors: Vincent
authors: V
authors: Van Pesch
authors: Department of Neurology, Orbis Medical Center, Sittard, the Netherlands.
authors: Raymond
authors: R
authors: Hupperts
authors: Department of Neurology, Hospital de Galdakao-Usansolo, Galdakao, Spain.
authors: José Luis
authors: JL
authors: Sánchez-Menoyo
authors: Department of Nephrology, Liverpool Hospital, Liverpool, Australia26Department of Neurology, Liverpool Hospital, Liverpool, Australia.
authors: Suzanne
authors: S
authors: Hodgkinson
authors: Department of Neurology, Jahn Ferenc Teaching Hospital, Budapest, Hungary.
authors: Csilla
authors: C
authors: Rozsa
authors: Neurology Unit, Groen Hart Ziekenhuis, Gouda, the Netherlands.
authors: Freek
authors: F
authors: Verheul
authors: Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia2Department of Medicine, University of Melbourne, Melbourne, Australia29Department of Neurology, Box Hill Hospital, Monash University, Melbourne, Australia.
authors: Helmut
authors: H
authors: Butzkueven
authors: Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia2Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Tomas
authors: T
authors: Kalincik
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine