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

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Multiple Sclerosis
Safety
Placebos
Fingolimod Hydrochloride
Recurrence
Therapeutics
Observational Studies
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis : 3-year results of the phase 2 extension study. / Saida, Takahiko; Itoyama, Yasuto; Kikuchi, Seiji; Hao, Qi; Kurosawa, Takayoshi; Ueda, Kengo; Auberson, Lixin Zhang; Tsumiyama, Isao; Nagato, Kazuo; Kira, Jun ichi.

In: BMC neurology, Vol. 17, No. 1, 17, 28.01.2017.

Research output: Contribution to journalArticle

Saida, Takahiko ; Itoyama, Yasuto ; Kikuchi, Seiji ; Hao, Qi ; Kurosawa, Takayoshi ; Ueda, Kengo ; Auberson, Lixin Zhang ; Tsumiyama, Isao ; Nagato, Kazuo ; Kira, Jun ichi. / Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis : 3-year results of the phase 2 extension study. In: BMC neurology. 2017 ; Vol. 17, No. 1.
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title = "Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis: 3-year results of the phase 2 extension study",
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).",
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T1 - Long-term efficacy and safety of fingolimod in Japanese patients with relapsing multiple sclerosis

T2 - 3-year results of the phase 2 extension study

AU - Saida, Takahiko

AU - Itoyama, Yasuto

AU - Kikuchi, Seiji

AU - Hao, Qi

AU - Kurosawa, Takayoshi

AU - Ueda, Kengo

AU - Auberson, Lixin Zhang

AU - Tsumiyama, Isao

AU - Nagato, Kazuo

AU - Kira, Jun ichi

PY - 2017/1/28

Y1 - 2017/1/28

N2 - 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).

AB - 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).

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