title: Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis.
abstract: OBJECTIVE
  In patients suffering multiple sclerosis activity despite treatment with interferon β or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no studies have directly compared the outcomes of switching to either of these agents.
  
  
  METHODS
  Using MSBase, a large international, observational, prospectively acquired cohort study, we identified patients with relapsing-remitting multiple sclerosis experiencing relapses or disability progression within the 6 months immediately preceding switch to either natalizumab or fingolimod. Quasi-randomization with propensity score-based matching was used to select subpopulations with comparable baseline characteristics. Relapse and disability outcomes were compared in paired, pairwise-censored analyses.
  
  
  RESULTS
  Of the 792 included patients, 578 patients were matched (natalizumab, n = 407; fingolimod, n = 171). Mean on-study follow-up was 12 months. The annualized relapse rates decreased from 1.5 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in relapse hazard (p = 0.002). A 2.8 times higher rate of sustained disability regression was observed after the switch to natalizumab in comparison to fingolimod (p < 0.001). No difference in the rate of sustained disability progression events was observed between the groups. The change in overall disability burden (quantified as area under the disability-time curve) differed between natalizumab and fingolimod (-0.12 vs 0.04 per year, respectively, p < 0.001).
  
  
  CONCLUSIONS
  This study suggests that in active multiple sclerosis during treatment with injectable disease-modifying therapies, switching to natalizumab is more effective than switching to fingolimod in reducing relapse rate and short-term disability burden.
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.forename: Vilija
authors.initials: V
authors.lastname: Jokubaitis
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Guillermo
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authors.lastname: Izquierdo
authors.forename: Csilla
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authors.lastname: Rozsa
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Marc
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authors.lastname: Girard
authors.forename: Eugenio
authors.initials: E
authors.lastname: Pucci
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez-Bolanos
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'Maison
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hodgkinson
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Daniele
authors.initials: D
authors.lastname: Spitaleri
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.forename: Murat
authors.initials: M
authors.lastname: Terzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Pamela
authors.initials: P
authors.lastname: McCombe
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez-Menoyo
authors.forename: Magdolna
authors.initials: M
authors.lastname: Simo
authors.forename: Tunde
authors.initials: T
authors.lastname: Csepany
authors.forename: Gabor
authors.initials: G
authors.lastname: Rum
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D012008:Recurrence; D012042:Registries; D012720:Severity of Illness Index; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine