title: The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis.
abstract: OBJECTIVE
  We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS).
  
  
  METHODS
  MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence.
  
  
  RESULTS
  A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation.
  
  
  CONCLUSIONS
  Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications.
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Warrender-Sparkes
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Tim
authors.initials: T
authors.lastname: Spelman
authors.affiliation: Hospital Universitario Virgen Macarena, Sevilla, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.affiliation: Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
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: Neuro Rive-Sud, Hôpital Charles LeMoyne, Quebec, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Grand'Maison
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine, General University Hospital and Charles University in Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Havrdova
authors.affiliation: Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine, General University Hospital and Charles University in Prague, Czech Republic.
authors.forename: Dana
authors.initials: D
authors.lastname: Horakova
authors.affiliation: Karadeniz Technical University, Trabzon, Turkey.
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.affiliation: University Hospital San Carlos, IdISSC, Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.affiliation: Amiri Hospital, Kuwait City, Kuwait.
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.affiliation: Ospedali Riuniti di Salerno, Salerno, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.affiliation: Hôpital Notre-Dame, Montreal, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.affiliation: Hôpital Notre-Dame, Montreal, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Girard
authors.affiliation: Ondokuz Mayis Üniversitesi, Samsun, Turkey.
authors.forename: Murat
authors.initials: M
authors.lastname: Terzi
authors.affiliation: Orbis Medicle Center, Sittard, The Netherlands.
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.affiliation: Hotel-Dieu de Levis, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.affiliation: Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.affiliation: Hospital Universitario Virgen de Valme, Seville, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez-Bolaños
authors.affiliation: FLENI, Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Fiol
authors.affiliation: Ospedale di Macerata, Macerata, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Pucci
authors.affiliation: John Hunter Hospital, Newcastle, Australia.
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.affiliation: Groen Hart Ziekenhuis, Gouda, The Netherlands.
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.affiliation: Hospital Italiano, Buenos Aires, Argentina.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Cristiano
authors.affiliation: Cliniques Universitaires Saint-Luc, Brussels, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.affiliation: Neurology Clinical Center, Skopje, Macedonia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Petkovska-Boskova
authors.affiliation: Jewish General Hospital, Montreal, Canada.
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.affiliation: New York University Langone Medical Center, New York, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Kister
authors.affiliation: National Neurological Institute C. Mondino, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.affiliation: INEBA, Buenos Aires, Argentina.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Saladino
authors.affiliation: Flinders University and Medical Centre, Adelaide, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.affiliation: Brain and Mind Research Institute, Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.affiliation: Department NEUROFARBA, Section of Neurosciences, University of Florence, Florence, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.affiliation: Geelong Hospital, Geelong, Australia.
authors.forename: Cameron
authors.initials: C
authors.lastname: Shaw
authors.affiliation: St Vincent's Hospital, Melbourne, Australia.
authors.forename: Neil
authors.initials: N
authors.lastname: Shuey
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, Liverpool, United Kingdom.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Young
authors.affiliation: Craigavon Area Hospital, Portadown, United Kingdom.
authors.forename: Orla
authors.initials: O
authors.lastname: Gray
authors.affiliation: University Hospital Basel, Neurology, Departments of Medicine, Clinical Research and Biomedicine, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia/ Department of Neurology, Box Hill Hospital, Monash University, Box Hill, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
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.affiliation: Department of Medicine, University of Melbourne, Melbourne, Australia vilija.jokubaitis@unimelb.edu.au.
authors.forename: Vilija
authors.initials: V
authors.lastname: Jokubaitis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003711:Demyelinating Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D057915:Drug Substitution; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride
keywords: MSBase; Multiple sclerosis; disease-modifying therapy; fingolimod; medication persistence