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, Giancarlo Comi, Hans Peter Hartung, Xavier Montalban, Jean Pelletier, Tracy Stites, Shannon Ritter, Philipp Von Rosenstiel, Davorka Tomic, Ludwig Kappos

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)468-475
Number of pages8
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume87
Issue number5
DOIs
Publication statusPublished - 1 May 2016

Cite this

Cohen, Jeffrey A. ; Khatri, Bhupendra ; Barkhof, Frederik ; Comi, Giancarlo ; Hartung, Hans Peter ; Montalban, Xavier ; Pelletier, Jean ; Stites, Tracy ; Ritter, Shannon ; Von Rosenstiel, Philipp ; Tomic, Davorka ; Kappos, Ludwig. / Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis : Results from the extension of the randomised TRANSFORMS study. In: Journal of Neurology, Neurosurgery and Psychiatry. 2016 ; Vol. 87, No. 5. pp. 468-475.
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title = "Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: Results from the extension of the randomised TRANSFORMS study",
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.",
author = "Cohen, {Jeffrey A.} and Bhupendra Khatri and Frederik Barkhof and Giancarlo Comi and Hartung, {Hans Peter} and Xavier Montalban and Jean Pelletier and Tracy Stites and Shannon Ritter and {Von Rosenstiel}, Philipp and Davorka Tomic and Ludwig Kappos",
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Cohen, JA, Khatri, B, Barkhof, F, Comi, G, Hartung, HP, Montalban, X, Pelletier, J, Stites, T, Ritter, S, Von Rosenstiel, P, Tomic, D & Kappos, L 2016, '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, vol. 87, no. 5, pp. 468-475. https://doi.org/10.1136/jnnp-2015-310597

Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis : Results from the extension of the randomised TRANSFORMS study. / Cohen, Jeffrey A.; Khatri, Bhupendra; Barkhof, Frederik; Comi, Giancarlo; Hartung, Hans Peter; Montalban, Xavier; Pelletier, Jean; Stites, Tracy; Ritter, Shannon; Von Rosenstiel, Philipp; Tomic, Davorka; Kappos, Ludwig.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 87, No. 5, 01.05.2016, p. 468-475.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis

T2 - Results from the extension of the randomised TRANSFORMS study

AU - Cohen, Jeffrey A.

AU - Khatri, Bhupendra

AU - Barkhof, Frederik

AU - Comi, Giancarlo

AU - Hartung, Hans Peter

AU - Montalban, Xavier

AU - Pelletier, Jean

AU - Stites, Tracy

AU - Ritter, Shannon

AU - Von Rosenstiel, Philipp

AU - Tomic, Davorka

AU - Kappos, Ludwig

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

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U2 - 10.1136/jnnp-2015-310597

DO - 10.1136/jnnp-2015-310597

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