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.

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Figures

Figure 1

Patient disposition.

Figure 2

Time to first confirmed relapse up to the end of the study (core intent to treat (ITT) population).

Figure 3

Annualised relapse rate of completers versus non-completers over time. *Number of patients who completed the study during M36–48. #Interval non-completers are patients who did not continue to the next yearly time interval. For interval non-completers, M0–24 summarises the aggregate ARR from M0 to M24 for patients who discontinued during the interval of M12–24. M0–36 summarises the aggregate ARR from M0 to M36 for patients who discontinued during the interval of M24–36. M0–48 summarises the aggregate ARR from M0 to M48 for patients who discontinued during the interval of M36–48. ARR, annualised relapse rate; IFN, interferon; M, month.

Figure 4

Between-group comparison of cumulative PBVC from core baseline. ***p

Figure 5

Comparison of NEDA status in the core study and the first extension year by treatment group (A) IFN-switch group (B) Continuous-fingolimod group. Data presented here are for the pooled fingolimod 0.5 and 1.25 mg groups. N, total number of patients in the group; n, number of patients achieving NEDA; IFN, interferon; NEDA, no evidence of disease activity.