Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study

Jeffrey A. Cohen , Bhupendra Khatri , Frederik Barkhof (1) , Giancarlo Comi (2) , Hans-Peter Hartung (3) , Xavier Montalban (4, 5) , Jean Pelletier (6, 7) , Tracy Stites , Shannon Ritter , Philipp Von Rosenstiel , Davorka Tomic , Ludwig Kappos (8) , Transforms (trial Assessing Injectable Interferon Vs. Fty720 Oral In Rrms) Study Group

1 VU University Medical Center [Amsterdam]
2 Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute,
3 Department of Neurology
4 MIAC AG - Medical Image Analysis Center
5 Vall d'Hebron University Hospital [Barcelona]
6 CRMBM - Centre de résonance magnétique biologique et médicale
7 APHM - Assistance Publique - Hôpitaux de Marseille
8 Department of Neurology [Suisse]

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.

Mots clés: Adult; Disability Evaluation; Double-Blind Method; Female; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Interferon beta-1a; Magnetic Resonance Imaging; Male; Multiple Sclerosis; Relapsing-Remitting; Neuroimaging; Recurrence; Treatment Outcome; Young Adult

Domaines: Ingénierie biomédicale

Jeffrey A. Cohen, Bhupendra Khatri, Frederik Barkhof, Giancarlo Comi, Hans-Peter Hartung, et al.. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. Journal of Neurology, Neurosurgery and Psychiatry, 2016, 87 (5), pp.468--475. ⟨10.1136/jnnp-2015-310597⟩. ⟨hal-01419490⟩