title: Predictors of long-term disability accrual in relapse-onset multiple sclerosis.
abstract: To identify predictors of 10-year Expanded Disability Status Scale (EDSS) change after treatment initiation in patients with relapse-onset multiple sclerosis.
  
  
  
  Using data obtained from MSBase, we defined baseline as the date of first injectable therapy initiation. Patients need only have remained on injectable therapy for 1 day and were monitored on any approved disease-modifying therapy, or no therapy thereafter. Median EDSS score changes over a 10-year period were determined. Predictors of EDSS change were then assessed using median quantile regression analysis. Sensitivity analyses were further performed.
  
  
  
  We identified 2,466 patients followed up for at least 10 years reporting post-baseline disability scores. Patients were treated an average 83% of their follow-up time. EDSS scores increased by a median 1 point (interquartile range = 0-2) at 10 years post-baseline. Annualized relapse rate was highly predictive of increases in median EDSS over 10 years (coeff = 1.14, p = 1.9 × 10(-22) ). On-therapy relapses carried greater burden than off-therapy relapses. Cumulative treatment exposure was independently associated with lower EDSS at 10 years (coeff = -0.86, p = 1.3 × 10(-9) ). Furthermore, pregnancies were also independently associated with lower EDSS scores over the 10-year observation period (coeff = -0.36, p = 0.009).
  
  
  
  We provide evidence of long-term treatment benefit in a large registry cohort, and provide evidence of long-term protective effects of pregnancy against disability accrual. We demonstrate that high annualized relapse rate, particularly on-treatment relapse, is an indicator of poor prognosis. Ann Neurol 2016;80:89-100.
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.|Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Vilija G
authors.identifier: 0000-0002-3942-4340
authors.initials: VG
authors.lastname: Jokubaitis
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.|Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Tomas
authors.identifier: 0000-0003-3778-1376
authors.initials: T
authors.lastname: Kalincik
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.|Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: Johannes
authors.initials: J
authors.lastname: Lorscheider
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, General University Hospital and Charles University in Prague, Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.affiliation: Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montreal, Quebec, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Girard
authors.affiliation: Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montreal, Quebec, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Centre de réadaptation déficience physique Chaudière-Appalache, Lévis, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.affiliation: Neurology Unit, Azienda Sanitaria Unica Regionale Marche AV3, Macerata, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Pucci
authors.affiliation: Neuro Rive-Sud, Charles LeMoyne Hospital, Greenfield Park, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Grand'Maison
authors.affiliation: Zuyderland Ziekenhuis, Sittard, The Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: University of Parma, Parma, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Granella
authors.affiliation: Nuovo Ospedale Civile S.Agostino/Estense, Modena, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sola
authors.affiliation: C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.affiliation: Ospedali Riuniti di Salerno, Salerno, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.affiliation: Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati, Avellino, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Spitaleri
authors.affiliation: Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.affiliation: Department of Neurology, Liverpool Hospital, Liverpool, New South Wales, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hodgkinson
authors.affiliation: Donostia Hospital, San Sebastián, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Olascoaga
authors.affiliation: Groene Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.affiliation: Centre for Clinical Research, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Pamela
authors.initials: P
authors.lastname: McCombe
authors.affiliation: Kommunehospitalet, Arhus C, Denmark.
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Jahn Ferenc Teaching Hospital, Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Rozsa
authors.affiliation: John Hunter Hospital, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.affiliation: Instituto de Neurociencias Buenos Aires, Buenos Aires, Argentina.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Saladino
authors.affiliation: MS Center, Department of Neuroscience, Imaging and Clinical Sciences, G. d'Annunzio University, Chieti, Italy.
authors.forename: Deborah
authors.initials: D
authors.lastname: Farina
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Iaffaldano
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Paolicelli
authors.affiliation: Department of Medicine and Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia.|Department of Neurology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.|Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Victoria, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
authors.affiliation: Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum-University of Bologna, Bologna, Italy.|IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
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
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D005260:Female; D005500:Follow-Up Studies; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis* / Q000188:drug therapy; D011247:Pregnancy; D011379:Prognosis; D065840:Protective Factors; D012008:Recurrence; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000068717:Glatiramer Acetate; D016899:Interferon-beta