TY - JOUR
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
N1 - Funding Information:
This study was funded by Novartis Pharma KK and Mitsubishi Tanabe Pharma Corporation. Funding for medical writing and editorial support from Oxford PharmaGenesis, Oxford, UK was provided by Novartis Pharma KK and Mitsubishi Tanabe Pharma Corporation.
Funding Information:
TS has received funding from, held board membership, spoken at scientific meetings, prepared manuscripts and has had consulting agreements in the past years with Novartis Pharma KK, Mitsubishi Tanabe Pharma Corporation, Kaketsuken, Biogen Japan, Astelas Pharma, Bayer, Merck-Serono, Nihon Pharmaceutical, Daiich-Sankyo, Ono Pharmaceutical, TDS Japan, Teijin Farma and Sanofi. YI has received research support from the Ministry of Education, Science and Technology of Japan; the Ministry of Health, Labor and Welfare of Japan, and honoraria from Bayer Schering Pharma and Biogen Idec Japan. SK has received research support from Japan Agency for Medical Research and Development and has received honoraria from Otsuka Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Abbot Japan, Sumitomo Dainippon Pharma, Nihon Medi-Physics, Fujifilm RI Pharma, GlaxoSmithKline K.K., Eisai, Japan Blood Products Organization, Nihon Pharmaceutical, Kyowa Hakko Kirin and Takeda Pharmaceutical Ltd. QH has no conflicts of interest to disclose. TK KU and IT are employees of Novartis Pharma KK, Japan. LZ-A is an employees of Novartis Pharma AG, Switzerland. KN is an employee of Mitsubishi Tanabe Pharma Corporation Japan. JK is a consultant for Biogen Japan and Novartis Pharma AG and has received honoraria from Bayer Healthcare, Otsuka Pharmaceutical, Novartis Pharma KK and Mitsubishi Tanabe Pharma Corporation, and funding for a trip from Bayer Healthcare. He is funded by grants from the Ministry of Health, Labor and Welfare, Japan, the Japan Science and Technology Agency and the Ministry of Education, Culture, Science, Sports and Technology, Japan, Japan Blood Products Organization, Novartis Pharma KK and Takeda Pharmaceutical Ltd.
Publisher Copyright:
© 2017 The Author(s).
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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U2 - 10.1186/s12883-017-0794-5
DO - 10.1186/s12883-017-0794-5
M3 - Article
C2 - 28129749
AN - SCOPUS:85010644696
VL - 17
JO - BMC Neurology
JF - BMC Neurology
SN - 1471-2377
IS - 1
M1 - 17
ER -