title: Comparative efficacy of switching to natalizumab in active multiple sclerosis.
abstract: OBJECTIVE
  To compare treatment efficacy and persistence in patients who switched to natalizumab versus those who switched between glatiramer acetate (GA) and interferon-beta (IFNβ) after an on-treatment relapse on IFNβ or GA using propensity score matched real-world datasets.
  
  
  METHODS
  Patients included were registered in MSBase or the TYSABRI Observational Program (TOP), had relapsed on IFNβ or GA within 12 months prior to switching to another therapy, and had initiated natalizumab or IFNβ/GA treatment ≤6 months after discontinuing prior therapy. Covariates were balanced across post switch treatment groups by propensity score matching at treatment initiation. Relapse, persistence, and disability measures were compared between matched treatment arms in the total population (n = 869/group) and in subgroups defined by prior treatment history (IFNβ only [n = 578/group], GA only [n = 165/group], or both IFNβ and GA [n = 176/group]).
  
  
  RESULTS
  Compared to switching between IFNβ and GA, switching to natalizumab reduced annualized relapse rate in year one by 65-75%, the risk of first relapse by 53-82% (mean follow-up 1.7-2.2 years) and treatment discontinuation events by 48-65% (all P ≤ 0.001). In the total population, switching to natalizumab reduced the risk of confirmed disability progression by 26% (P = 0.036) and decreased the total disability burden by 1.54 EDSS-years (P < 0.0001) over the first 24 months post switch.
  
  
  CONCLUSIONS
  Using large, real-world, propensity-matched datasets we demonstrate that after a relapse on IFNβ or GA, switching to natalizumab (rather than between IFNβ and GA) led to superior outcomes for patients in all measures assessed. Results were consistent regardless of the prior treatment identity.
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne Melbourne, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne Melbourne, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.affiliation: Biogen Idec Inc. Cambridge, Massachusetts.
authors.forename: Annie
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.affiliation: Department of Neurology, University of Münster Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University Hospital Basel Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Biogen Idec Int BV Badhoevedorp, The Netherlands.
authors.forename: Larisa
authors.initials: L
authors.lastname: Tsvetkova
authors.affiliation: Biogen Idec Inc. Cambridge, Massachusetts.
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
authors.affiliation: Biogen Idec Inc. Cambridge, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Hyde
authors.affiliation: Groene Hart Ziekenhuis Gouda, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.affiliation: Neuro Rive-Sud, Hôpital Charles LeMoyne Quebec, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Grand-Maison
authors.affiliation: Hospital Universitario Virgen Macarena Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Center de réadaptation déficience physique Chaudière-Appalache Levis, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.affiliation: Hôpital Notre Dame Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.affiliation: MS Center, Department of Neuroscience, Imaging and Clinical Sciences, University "G. d'Annunzio" Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.affiliation: John Hunter Hospital Newcastle, Australia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.affiliation: University Hospital San Carlos Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.affiliation: Orbis Medical Centre Sittard-Geleen, The Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: Kommunehospitalet Arhus C, Denmark.
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Brain and Mind Research Institute Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne Melbourne, Australia ; Department of Neurology, Eastern Health, Monash University Box Hill, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven