title: Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs. interferon β-1a intramuscular: Subgroup analyses of the Trial Assessing Injectable Interferon vs. Fingolimod Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS).
abstract: BACKGROUND
  Fingolimod demonstrated superior efficacy compared with interferon β-1a intramuscular in relapsing multiple sclerosis. The impact of treatment history on fingolimod efficacy is unknown.
  
  
  OBJECTIVE
  This post-hoc analysis of phase 3 TRANSFORMS data compared the efficacy and safety of fingolimod and interferon β-1a intramuscular among patient subgroups defined by prior treatment history.
  
  
  METHODS
  Annualized relapse rate and safety of once-daily oral fingolimod 0.5mg, 1.25mg, or once-weekly interferon β-1a 30μg intramuscular for 12 months were analyzed in 1292 patients with relapsing multiple sclerosis according to prior disease-modifying therapy, reason for prior disease-modifying therapy discontinuation (adverse events or unsatisfactory therapeutic effect), and prior disease-modifying therapy duration.
  
  
  RESULTS
  Compared with interferon β-1a intramuscular, fingolimod 0.5mg significantly reduced annualized relapse rate in patients who were treatment naive, received prior interferon-β treatment, discontinued prior disease-modifying therapy for unsatisfactory therapeutic effect, or had prior disease-modifying therapy duration of ≥1 year (P≤0.05, all comparisons). Similar trends were observed in patients with prior glatiramer acetate treatment. Significant reductions were also seen with fingolimod 1.25mg for treatment-naive and prior interferon-β-treated patients.
  
  
  CONCLUSIONS
  This analysis demonstrates superiority of fingolimod over interferon β-1a intramuscular regardless of prior (interferon-β) treatment and prior treatment efficacy and duration. ClinicalTrials.gov identifier: NCT00340834.
authors: The Regional MS Center, Center for Neurological Disorders, Wheaton Franciscan Health Care, 3237 S. 16th Street, Milwaukee, WI 53215, USA. Electronic address: bokhatri@aol.com.
authors: B O
authors: BO
authors: Khatri
authors: CHU La Timone, CRMBM-CNRS 6612, Marseille, France. Electronic address: jean.pelletier@mail.ap-hm.fr.
authors: J
authors: J
authors: Pelletier
authors: University Hospital, Petersgraben 4, Basel 4031, Switzerland. Electronic address: lkappos@uhbs.ch.
authors: L
authors: L
authors: Kappos
authors: Heinrich Heine University, Moorenstr 5, Dusseldorf 40225, Germany. Electronic address: Hans-Peter.Hartung@uniduesseldorf.de.
authors: H-P
authors: HP
authors: Hartung
authors: Università Vita-Salute San Raffaele, Milan 20123, Italy. Electronic address: comi.giancarlo@unisr.it.
authors: G
authors: G
authors: Comi
authors: VU Medical Center, P.O. Box 7057, Amsterdam 1007 MB, The Netherlands. Electronic address: f.barkhof@vumc.nl.
authors: F
authors: F
authors: Barkhof
authors: Novartis Pharma AG, Kirschgarten Site, Basel 4002, Switzerland. Electronic address: philipp.von_rosenstiel@novartis.com.
authors: P
authors: P
authors: von Rosenstiel
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: Xiangyi.meng@novartis.com.
authors: X
authors: X
authors: Meng
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: augustogrinspan@hotmail.com.
authors: A
authors: A
authors: Grinspan
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: ronny.hashmonay@novartis.com.
authors: R
authors: R
authors: Hashmonay
authors: Mellen Center, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Electronic address: cohenj@ccf.org.
authors: J A
authors: JA
authors: Cohen
keywords: Disease-modifying therapy; Fingolimod; Interferon; Multiple sclerosis; Relapse rate; Sphingosine 1-phosphate receptor modulator