Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study

Takahiko Saida, Yasuto Itoyama, Seiji Kikuchi, Qi Hao, Takayoshi Kurosawa, Kengo Ueda, Lixin Zhang Auberson, Isao Tsumiyama, Kazuo Nagato, Jun ichi Kira

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Abstract

Background: The low level of disease activity and manageable safety profile seen with fingolimod versus placebo in a 6-month, phase 2, randomized controlled trial in Japanese patients with relapsing multiple sclerosis (MS; ClinicalTrials.gov Identifier NCT00537082) were maintained in the initial 6-month observational study extension. Here, we report long-term safety and efficacy results of the 3-year follow-up to the phase 2 study extension. Methods: The 6-month core study was completed by 147 patients, of whom 143 entered the extension and took at least one dose of fingolimod. Those originally randomized to placebo were re-randomized to fingolimod 1.25 mg (n = 23) or 0.5 mg (n = 27). During the extension, the patients taking fingolimod 1.25 mg (n = 46) were switched to open-label fingolimod 0.5 mg, and those originally randomized to fingolimod 0.5 mg (n = 47) continued with open-label fingolimod 0.5 mg. Results: Continuous fingolimod treatment was associated with a sustained low level of MRI and relapse activity for the duration of the extension phase; 75-100% (range across all assessment time points up to end of study) of patients remained free of Gd-enhanced T1 lesions, 88-100% remained free of new/newly enlarged T2 lesions, and 45-62% remained relapse-free. In patients who switched to the active treatment, a 79.5% decrease in annualized relapse rate (ARR; from 1.131 before switch to 0.232 6-months after switch) was observed in the first 6 months of the extension phase and thereafter remained low until the end of study (0.16-0.31 across all assessment time points after switch up to end of study). The mean number of Gd-enhanced T1 and new/newly enlarged T2 lesions decreased up to month 9 and thereafter remained low until the end of study (0.0-0.1 and 0.0-0.3, respectively, across all assessment time points after switch up to end of study). Fingolimod was generally well-tolerated and the safety profile was consistent with the core and 6-month extension. Serious adverse events were reported in 13.3% of patients during the extension study, with the range in the continuous fingolimod and placebo-fingolimod switch groups (3.7-21.7%) being similar to that reported in the core study for the placebo and fingolimod groups (5.3-20.4%). Conclusion: Continuous fingolimod treatment over 36 months was associated with maintained efficacy and a manageable safety profile with no new safety signals. These results indicate that fingolimod provides long-term treatment benefit for Japanese patients with relapsing MS. Trial registration: ClinicalTrials.gov NCT00670449(April 28, 2008).

Original languageEnglish
Article number17
JournalBMC neurology
Volume17
Issue number1
DOIs
Publication statusPublished - Jan 28 2017

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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    Saida, T., Itoyama, Y., Kikuchi, S., Hao, Q., Kurosawa, T., Ueda, K., Auberson, L. Z., Tsumiyama, I., Nagato, K., & Kira, J. I. (2017). Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study. BMC neurology, 17(1), [17]. https://doi.org/10.1186/s12883-017-0794-5