Article Text

Research paper
Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study
  1. Jeffrey A Cohen1,
  2. Bhupendra Khatri2,
  3. Frederik Barkhof3,
  4. Giancarlo Comi4,
  5. Hans-Peter Hartung5,
  6. Xavier Montalban6,
  7. Jean Pelletier7,
  8. Tracy Stites8,
  9. Shannon Ritter8,
  10. Philipp von Rosenstiel9,
  11. Davorka Tomic10,
  12. Ludwig Kappos11
  13. on behalf of the TRANSFORMS (TRial Assessing injectable interferoN vS. FTY720 Oral in RRMS) Study Group
  1. 1Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA
  2. 2Center for Neurological Disorders and the Regional MS Center at WFHC, Milwaukee, Wisconsin, USA
  3. 3Image Analysis Centre, VU University Medical Centre, Amsterdam, The Netherlands
  4. 4Department of Neurology, Vita-Salute San Raffaele University, Milan, Italy
  5. 5Department of Neurology, Heinrich Heine University, Düsseldorf, Germany
  6. 6Department of Neurology-Neuroimmunology, Vall d'Hebron University Hospital, Barcelona, Spain
  7. 7Department of Neurology and CRMBM CNRS6612, Aix Marseille Université, CHU La Timone, Marseille, France
  8. 8Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA
  9. 9Biogen, 14 Cambridge Center, Cambridge, Massachusetts, USA
  10. 10Novartis Pharma AG, Basel, Switzerland
  11. 11Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Basel, Switzerland
  1. Correspondence to Professor Ludwig Kappos, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital, Basel 4031, Switzerland; lkappos{at}uhbs.ch

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.

Clinical trial registration No NCT00340834.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Statistics from Altmetric.com

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.