Marcelo Kremenchutzky1, Paul O'Connor2, Reinhard Hohlfeld3, Lixin Zhang-Auberson4, Philipp von Rosenstiel5, Xiangyi Meng6, Augusto Grinspan7, Ron Hashmonay8, Ludwig Kappos9. 1. London (Ont) MS Clinic, Western University, 339 Windermere Road, London, ON, Canada N6A6A5. Electronic address: marcelo.kremenchutzky@LHSC.ON.CA. 2. St. Michael's Hospital, 30 Bond Street, Suite 3 007 Shuter Wing, Toronto, ON, Canada M5B1W8. Electronic address: oconnorp@smh.toronto.on.ca. 3. Institut fur Klinische Neuroimmunologie, University of Munich, Marchioninistr 15, Munich D-81377, Germany. Electronic address: reinhard.hohlfeld@med.uni-muenchen.de. 4. Novartis Pharma AG, Basel 4002, Switzerland. Electronic address: lixin.zhang_auberson@novartis.com. 5. Novartis Pharma AG, Basel 4002, Switzerland. Electronic address: philipp.von_rosenstiel@novartis.com. 6. Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: Xiangyi.meng@novartis.com. 7. Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: augustogrinspan@hotmail.com. 8. Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936, USA. Electronic address: ronny.hashmonay@novartis.com. 9. University Hospital, Petersgraben 4, Basel 4031, Switzerland. Electronic address: lkappos@uhbs.ch.
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.
RCT Entities:
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 sclerosispatients, 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 sclerosispatients regardless of prior treatment history. Clinicaltrials.gov identifier: NCT00289978.
Authors: Oscar Fernández; Guillermo Izquierdo; Eduardo Aguera; Cristina Ramo; Miguel Hernandez; Diego Silva; Rob Walker; Helmut Butzkueven; Chenyu Wang; Michael Barnett Journal: Mult Scler J Exp Transl Clin Date: 2020-09-13