title: Factors influencing long-term outcomes in relapsing-remitting multiple sclerosis: PRISMS-15.
abstract: OBJECTIVE
  An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  Patients in the original PRISMS study were invited to a single follow-up visit 15 years after initial randomisation (PRISMS-15). Outcomes over 15 years were compared in the lowest and highest quartile of the cumulative sc IFN β-1a dose groups, and according to total time receiving sc IFN β-1a as a continuous variable per 5 years of treatment. Potential prognostic factors for outcomes were analysed.
  
  
  RESULTS
  Of 560 patients randomised in PRISMS, 291 returned for PRISMS-15 and 290 (51.8%) were analysed. Higher cumulative dose exposure and longer treatment time appeared to be associated with better outcomes on: annualised relapse rate, number of relapses, time to Expanded Disability Status Scale (EDSS) progression, change in EDSS, proportions of patients with EDSS ≥ 4 or ≥ 6, ≤ 5 relapses and EDSS <4 or <6, and time to conversion to secondary-progressive MS (SPMS). Higher dose exposure was associated with lower proportions of patients with EDSS progression and conversion to SPMS, and longer time on treatment with lower risk of first relapse. Change in EDSS from baseline to 24 months was a strong predictor of evaluated clinical outcomes over 15 years.
  
  
  CONCLUSIONS
  These findings suggest that higher cumulative exposure to sc IFN β-1a may be associated with better clinical outcomes, and early change in EDSS score may have prognostic value, over many years, in RRMS.
authors.affiliation: Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Neurology, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital Basel, Basel, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.affiliation: Helsinki MS Center/The Finnish MS Society, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Multanen
authors.affiliation: MS Clinic, University Hospital, London Health Sciences Centre, London, Ontario, Canada.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kremenchutzky
authors.affiliation: Global Clinical Development Unit, Merck Serono SA, Geneva, Switzerland.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Verdun di Cantogno
authors.affiliation: Global Biostatistics, Merck Serono SA, Geneva, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Cornelisse
authors.affiliation: Global Clinical Development Unit, Merck Serono SA, Geneva, Switzerland.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Lehr
authors.affiliation: Global Biostatistics, EMD Serono, Inc, Rockland, Massachusetts, USA.
authors.forename: Florence
authors.initials: F
authors.lastname: Casset-Semanaz
authors.affiliation: Cytel Inc, Geneva, Switzerland.
authors.forename: Delphine
authors.initials: D
authors.lastname: Issard
authors.affiliation: VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Bernard M J
authors.initials: BM
authors.lastname: Uitdehaag
mesh_terms: D000328:Adult; D000368:Aged; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000068556:Interferon beta-1a / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000628:therapy*; D061214:Patient Safety; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000068556:Interferon beta-1a
keywords: INTERFERON; MRI; MULTIPLE SCLEROSIS