title: Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study.
abstract: OBJECTIVE
  The 12-month (M), phase 3, double-blind, randomised TRANSFORMS study demonstrated significant benefits of fingolimod 0.5 or 1.25 mg over interferon β-1a (IFNβ-1a) in patients with relapsing-remitting multiple sclerosis. We report the results of long-term (up to 4.5 years) extension of TRANSFORMS.
  
  
  METHODS
  Patients randomised to fingolimod (0.5/1.25 mg) in the core phase continued the same dose (continuous-fingolimod) in the extension, whereas those on IFNβ-1a were re-randomised (1:1) to fingolimod (IFN-switch; IFN: 0.5/1.25 mg). Outcomes included annualised relapse rate (ARR), confirmed disability progression and MRI measures. Results are presented here for the continuous-fingolimod 0.5 mg and pooled IFN-switch groups.
  
  
  RESULTS
  Of the 1027 patients who entered the extension, 772 (75.2%) completed the study. From baseline to the end of the study (EOS), ARR in patients on continuous-fingolimod 0.5 mg was significantly lower than in the IFN-switch group (M0-EOS: 0.17 vs 0.27). After switching to fingolimod (M0-12 vs M13-EOS), patients initially treated with IFN had a 50% reduction in ARR (0.40 vs 0.20), reduced MRI activity and a lower rate of brain volume loss. In a post hoc analysis, the proportion of IFN-switch patients with no evidence of disease activity increased by approximately 50% in the first year after switching to fingolimod treatment (44.3% to 66.0%). The safety profile was consistent with that observed in the core phase.
  
  
  CONCLUSIONS
  These results support a continued effect of long-term fingolimod therapy in maintaining a low rate of disease activity and sustained improved efficacy after switching from IFNβ-1a to fingolimod.
  
  
  BACKGROUND
  NCT00340834.
authors.affiliation: Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cohen
authors.affiliation: Center for Neurological Disorders and the Regional MS Center at WFHC, Milwaukee, Wisconsin, USA.
authors.forename: Bhupendra
authors.initials: B
authors.lastname: Khatri
authors.affiliation: Image Analysis Centre, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Neurology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.affiliation: Department of Neurology-Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: Department of Neurology and CRMBM CNRS6612, Aix Marseille Université, CHU La Timone, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Stites
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Ritter
authors.affiliation: Biogen, 14 Cambridge Center, Cambridge, Massachusetts, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: von Rosenstiel
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Davorka
authors.initials: D
authors.lastname: Tomic
authors.affiliation: Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D000068556:Interferon beta-1a / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D059906:Neuroimaging; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D000068876:Fingolimod Hydrochloride; D000068556:Interferon beta-1a