title: Fingolimod after natalizumab and the risk of short-term relapse.
abstract: OBJECTIVE
  To determine early risk of relapse after switch from natalizumab to fingolimod; to compare the switch experience to that in patients switching from interferon-β/glatiramer acetate (IFN-β/GA) and those previously treatment naive; and to determine predictors of time to first relapse on fingolimod.
  
  
  METHODS
  Data were obtained from the MSBase Registry. Relapse rates (RRs) for each patient group were compared using adjusted negative binomial regression. Survival analyses coupled with adjusted Cox regression were used to model predictors of time to first relapse on fingolimod.
  
  
  RESULTS
  A total of 536 patients (natalizumab-fingolimod [n = 89]; IFN-β/GA-fingolimod [n = 350]; naive-fingolimod [n = 97]) were followed up for a median 10 months. In the natalizumab-fingolimod group, there was a small increase in RR on fingolimod (annualized RR [ARR] 0.38) relative to natalizumab (ARR 0.26; p = 0.002). RRs were generally low across all patient groups in the first 9 months on fingolimod (RR 0.001-0.13). However, 30% of patients with disease activity on natalizumab relapsed within the first 6 months on fingolimod. Independent predictors of time to first relapse on fingolimod were the number of relapses in the prior 6 months (hazard ratio [HR] 1.59 per relapse; p = 0.002) and a gap in treatment of 2-4 months compared to no gap (HR 2.10; p = 0.041).
  
  
  CONCLUSIONS
  RRs after switch to fingolimod were low in all patient groups. The strongest predictor of relapse on fingolimod was prior relapse activity. Based on our data, we recommend a maximum 2-month treatment gap for switches to fingolimod to decrease the hazard of relapse.
  
  
  METHODS
  This study provides Class IV evidence that RRs are not higher in patients with multiple sclerosis switching to fingolimod from natalizumab compared to those patients switching to fingolimod from other therapies.
authors.affiliation: From the Department of Medicine (V.G.J., T.K., H.B.), Melbourne Brain Centre (RMH), The University of Melbourne; Department of Neurology (V.G.J., V.L., T.K., H.B.), Royal Melbourne Hospital, Australia; Hospital Universitario Virgen Macarena (G.I.), Seville, Spain; Liverpool Hospital (S.H.), New South Wales, Australia; Amiri Hospital (R.A.), Kuwait City, Kuwait; John Hunter Hospital (J.L.-S.), Newcastle, Australia; MS Center (A.L.), Department of Neuroscience and Imaging, University "G. d'Annunzio," Chieti, Italy; Hôpital Notre Dame (P.D., M.G.), Montreal, Canada; Brain and Mind Research Institute (M.B.), Sydney, Australia; Neuro Rive-Sud (F.G.), Hôpital Charles LeMoyne, Quebec, Canada; Department of Basic Medical Sciences (M.T.), Neuroscience and Sense Organs, University of Bari, Italy; Flinders University and Medical Centre (M.S.), Adelaide, Australia; Ospedale di Macerata (G.G.), Italy; Geelong Hospital (C.S.), Australia; Karadeniz Technical University (C.B.), Trabzon, Turkey; AORN San Giuseppe Moscati (D.L.A.S.), Avellino, Italy; Groene Hart Ziekenhuis (F.V.), Gouda, the Netherlands; Department of Neurology (J.H., H.B.), Eastern Health Victoria; Monash University (J.H., H.B.), Melbourne; and Melbourne EpiCentre (D.L.), The University of Melbourne and Melbourne Health, Australia.
authors.forename: Vilija G
authors.initials: VG
authors.lastname: Jokubaitis
authors.forename: Vivien
authors.initials: V
authors.lastname: Li
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hodgkinson
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Marc
authors.initials: M
authors.lastname: Girard
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'Maison
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giuliani
authors.forename: Cameron
authors.initials: C
authors.lastname: Shaw
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.forename: Daniele L A
authors.initials: DL
authors.lastname: Spitaleri
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.forename: Jodi
authors.initials: J
authors.lastname: Haartsen
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016899:Interferon-beta / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000517:prevention & control; D000069442:Natalizumab; D011409:Propylene Glycols / Q000627:therapeutic use*; D012307:Risk Factors; D055502:Secondary Prevention; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D011409:Propylene Glycols; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine