Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12 months: results of a phase 2 observational extension

Jun-ichi Kira, Yasuto Itoyama, Seiji Kikuchi, Qi Hao, Takayoshi Kurosawa, Kazuo Nagato, Isao Tsumiyama, Philipp von Rosenstiel, Lixin Zhang-Auberson, Takahiko Saida, Jun-ichi Kira, Yasuto Itoyama, Seiji Kikuchi, Qi Hao, Takayoshi Kurosawa, Kazuo Nagato, Isao Tsumiyama, Philipp von Rosenstiel, Lixin Zhang-Auberson, Takahiko Saida

Abstract

Background: A 6-month phase 2 study of fingolimod demonstrated efficacy and safety in Japanese patients with relapsing-remitting multiple sclerosis (MS). Here we report a 6-month observational extension that evaluated efficacy and safety in patients who received fingolimod continuously for 12 months or who switched from placebo to fingolimod.

Methods: Of 147 patients who completed the 6-month core study, 143 entered the extension. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg or 0.5 mg. During the extension, all patients were switched to open-label fingolimod 0.5 mg.

Results: Magnetic resonance imaging (MRI) and relapse outcomes were maintained or improved in patients treated with fingolimod for 12 months versus those treated for 6 months. No new safety events were reported over 12 months of treatment. Infections occurred in similar proportions of continuously treated and switched patients, while cardiac and liver adverse events occurred in fewer continuously treated than switched patients. Four patients were aquaporin-4 (AQP4) antibody-positive, three of whom showed rapid disease exacerbations within 10 days of fingolimod initiation.

Conclusion: Continuous fingolimod treatment for up to 12 months was associated with maintained or improved efficacy and a manageable safety profile, consistent with that previously seen. Results in a small number of patients suggest lack of benefit in AQP4 antibody-positive patients. Meaningful statistical interpretation was limited by the small sample size in each treatment group, owing to the number of patients who completed the core study.

Trial registration: ClinicalTrials.gov NCT00670449.

Figures

Figure 1
Figure 1
Enrollment, randomization and follow-up of study patients.
Figure 2
Figure 2
Clinical and magnetic resonance imaging (MRI) endpoints over months 0–12. Between-groups comparisons for (A) proportions of patients who were free of new/newly enlarged T2 lesions, (B) proportions of patients who were relapse-free (absolute number of patients free of confirmed relapses), (C) the cumulative number of new/newly enlarged T2 lesions and (D) the annualized relapse rate (calculated as total number of confirmed relapses per treatment arm divided by total number of days on the study for all patients per treatment arm, multiplied by 365.25). The MRI analysis population was used for the proportion of patients free of new/newly enlarged T2 lesions (A) and cumulative number of new/newly enlarged T2 lesions (C). The extension full analysis set was used for the proportion of patients relapse-free (B) and annualized relapse rate (D).
Figure 3
Figure 3
Kaplan-Meier plot of time to first confirmed relapse up to month 12 (extension full analysis set).

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Source: PubMed

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