title: Impact of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod: Subgroup analyses of the Fingolimod Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) study.
abstract: BACKGROUND
  Fingolimod is a once-daily, oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing multiple sclerosis.
  
  
  OBJECTIVE
  This post-hoc analysis of phase 3 FREEDOMS data assessed whether the effects of fingolimod are consistent among subgroups of patients defined by prior treatment history.
  
  
  METHODS
  Annualized relapse rate and safety profile of treatment with fingolimod 0.5mg, 1.25mg, or placebo once-daily for 24 months were analyzed in 1272 relapsing multiple sclerosis patients, by subgroups based on disease-modifying therapy history (treatment-naive; prior interferon-β or glatiramer acetate), reason for discontinuation of prior disease-modifying therapy (unsatisfactory therapeutic response or adverse events), and prior disease-modifying therapy duration.
  
  
  RESULTS
  Both fingolimod doses significantly reduced annualized relapse rate in patients that received prior interferon-β or glatiramer acetate, discontinued prior disease-modifying therapy owing to unsatisfactory therapeutic effect, were treatment-naive, or had prior disease-modifying therapy duration of >1-3 years (P≤0.0301 for all comparisons vs placebo). Fingolimod 1.25mg resulted in greater reductions in annualized relapse rate in patients that discontinued prior disease-modifying therapy for adverse events or had prior disease-modifying therapy duration of ≤1 year or >3 years (P≤0.0194 vs placebo).
  
  
  CONCLUSIONS
  Fingolimod demonstrated similar efficacy in relapsing multiple sclerosis patients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978.
authors: London (Ont) MS Clinic, Western University, 339 Windermere Road, London, ON, Canada N6A6A5. Electronic address: marcelo.kremenchutzky@LHSC.ON.CA.
authors: Marcelo
authors: M
authors: Kremenchutzky
authors: St. Michael's Hospital, 30 Bond Street, Suite 3 007 Shuter Wing, Toronto, ON, Canada M5B1W8. Electronic address: oconnorp@smh.toronto.on.ca.
authors: Paul
authors: P
authors: O'Connor
authors: Institut fur Klinische Neuroimmunologie, University of Munich, Marchioninistr 15, Munich D-81377, Germany. Electronic address: reinhard.hohlfeld@med.uni-muenchen.de.
authors: Reinhard
authors: R
authors: Hohlfeld
authors: Novartis Pharma AG, Basel 4002, Switzerland. Electronic address: lixin.zhang_auberson@novartis.com.
authors: Lixin
authors: L
authors: Zhang-Auberson
authors: Novartis Pharma AG, Basel 4002, Switzerland. Electronic address: philipp.von_rosenstiel@novartis.com.
authors: Philipp
authors: P
authors: von Rosenstiel
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: Xiangyi.meng@novartis.com.
authors: Xiangyi
authors: X
authors: Meng
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: augustogrinspan@hotmail.com.
authors: Augusto
authors: A
authors: Grinspan
authors: Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: ronny.hashmonay@novartis.com.
authors: Ron
authors: R
authors: Hashmonay
authors: University Hospital, Petersgraben 4, Basel 4031, Switzerland. Electronic address: lkappos@uhbs.ch.
authors: Ludwig
authors: L
authors: Kappos
keywords: Disease-modifying therapy; Fingolimod; Multiple sclerosis; Relapse rate; Sphingosine 1-phosphate receptor modulator; Treatment history