TY - JOUR
T1 - Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis
T2 - An open-label, long-term extension study
AU - Yamanaka, Hisashi
AU - Tanaka, Yoshiya
AU - Takeuchi, Tsutomu
AU - Sugiyama, Naonobu
AU - Yuasa, Hirotoshi
AU - Toyoizumi, Shigeyuki
AU - Morishima, Yosuke
AU - Hirose, Tomohiro
AU - Zwillich, Samuel
N1 - Funding Information:
The authors would like to thank the patients who were involved in this study, the A3921041 investigators and study team. The authors would like to acknowledge Makoto Suzuki, Hiroyuki Nakamura, Keiko Yazawa, and Yukako Ohno for their valuable contribution to the study. This study was sponsored by Pfizer Inc. Editorial support under the direction of the authors was provided by Karen Irving and Daniel Binks, PhD, of Complete Medical Communications and was funded by Pfizer Inc. The specific ethical bodies that approved study A3921041 are as follows: National Hospital Organization Chiba-East Hospital, Chiba; The University of Tokyo Hospital IRB, Tokyo; National Hospital Organization Sagamihara National Hospital, Kanagawa; Niigata University Medical & Dental Hospital IRB, Niigata; National Hospital Organization Osaka Minami Center, Osaka; University of Occupational and Environmental Health Hospital IRB, Fukuoka; Tokyo Women’s Medical University Hospital IRB, Tokyo; Tokyo Medical and Dental University Hospital, Faculty of Medicine IRB, Tokyo; IRB of Saitama Medical Center, Saitama Medical University, Saitama; National Hospital Organization Murayama Medical Center IRB, Tokyo; Kumamoto Saishunso National Hospital IRB, Kumamoto; Taga General Hospital IRB, Ibaraki; Juntendo Tokyo Koto Geriatric Medical Center IRB, Tokyo; National Hospital Organization Tokyo Medical Center IRB, Tokyo; Sasaki Foundation Kyoundo Hospital IRB, Tokyo; National Hospital Organization Kyushu Medical Center IRB, Fukuoka; NS Clinic IRB, Tokyo; Juntendo University Hospital IRB, Tokyo; Kitasato University Kitasato Institute Medical Center Hospital IRB, Saitama; Fukushimadaiichi Hospital IRB, Fukushima; Chiba-ken Saiseikai Narashino Hospital IRB, Chiba; Sone Clinic IRB, Tokyo; Aso Iizuka Hospital, Fukuoka; Medical Co. LTA Kyushu Clinical Pharmacology Research Clinic IRB, Fukuoka; National Hospital Organization Central Review Board, Tokyo; Sasebo Chuo Hospital IRB, Nagasaki; Haradoi Hospital IRB, Fukuoka; Sapporo City General Hospital IRB, Hokkaido; Nagoya University Hospital IRB, Aichi; Hokkaido University Hospital IRB, Hokkaido; Hokkaido Medical Center for Rheumatic Diseases IRB, Hokkaido; Toyooka Chuo Hospital, Hokkaido; Tsukuba University Hospital IRB, Ibaraki; Kumamoto Orthopaedic Hospital IRB, Kumamoto; Higashihiroshima Memorial Hospital IRB, Hiroshima; Kyoto University Hospital IRB, Kyoto; Nagasaki University Hospital IRB, Nagasaki; The Hospital of Hyogo College of Medicine IRB, Hyogo; Inoue Hospital IRB, Gunma; Keihin Central Clinic, Hisamitsu Clinic and Masabayashi Clinic IRB, Tokyo; Hanna Hospital IRB, Osaka; IRB of St. Mary’s Hospital, Fukuoka; Wakaba Hospital IRB, Saitama; Kitano Hospital IRB, Osaka; University Hospital, Kyoto Prefectural University of Medicine IRB, Kyoto; Hiroshima Red Cross & Atomic-Bomb Survivors Hospital IRB, Hiroshima; Keio University Hospital IRB, Tokyo; Hamamatsu Clinical Research Network IRB, Shizuoka, Japan.
Publisher Copyright:
© 2016 Yamanaka et al.
PY - 2016/1/28
Y1 - 2016/1/28
N2 - Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Methods: Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. Results: A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Conclusions: Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Trial registration: Clinicaltrials.gov NCT00661661. Registered 7 February 2008.
AB - Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Here, tofacitinib safety and efficacy data from a long-term extension study in Japanese patients are presented. Methods: Study A3921041 was a multi-centre, open-label, long-term extension study that included Japanese patients who had participated in a prior Phase 2 or Phase 3 study of tofacitinib as monotherapy or with background methotrexate. Patients received tofacitinib 5 mg twice daily (BID) or tofacitinib 10 mg BID. Dose adjustment of tofacitinib during treatment period, and concomitant usage of disease-modifying antirheumatic drugs including methotrexate after week 12 were permitted. Primary endpoints were adverse events, laboratory parameters and vital signs. Secondary efficacy endpoints included American College of Rheumatology (ACR)20/50/70 response rates, Disease Activity Score (DAS)28-4(erythrocyte sedimentation rate (ESR))<2.6 response rate (DAS-defined remission) and Health Assessment Questionnaire-Disability Index (HAQ-DI) score. Safety and efficacy data were assessed throughout the study. Results: A total of 486 patients were recruited and treated (1439.9 patient-years of exposure). 308 patients completed the study. Median (range) duration of treatment in this extension study was 1185 (5-2016) days. 476 patients (97.9 %) experienced adverse events; the majority of which (97.8 %) were of mild or moderate severity. The two most common treatment-emergent adverse events were nasopharyngitis (n = 293, 60.3 %) and herpes zoster (n = 94, 19.3 %). For all tofacitinib-treated patients, the incidence rate (patients with events per 100 patient-years) was 10.7 for serious adverse events, 3.3 for serious infections, 7.4 for herpes zoster (serious and non-serious) and 1.2 for malignancies (excluding non-melanoma skin cancer). Mean changes from baseline (start of the index study) in laboratory parameters were consistent with those seen in previously reported studies of tofacitinib. ACR20/50/70 response rates, DAS-defined remission rates and HAQ-DI scores were sustained through to study completion. Conclusions: Tofacitinib (with or without background methotrexate) demonstrated a stable safety profile and sustained efficacy in Japanese patients with active rheumatoid arthritis. The risk of herpes zoster appears to be higher in Japanese patients treated with tofacitinib than in the global population. Trial registration: Clinicaltrials.gov NCT00661661. Registered 7 February 2008.
KW - Japanese
KW - Long-term extension
KW - Rheumatoid arthritis
KW - Tofacitinib
UR - http://www.scopus.com/inward/record.url?scp=84957818542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957818542&partnerID=8YFLogxK
U2 - 10.1186/s13075-016-0932-2
DO - 10.1186/s13075-016-0932-2
M3 - Article
C2 - 26818974
AN - SCOPUS:84957818542
SN - 1478-6354
VL - 18
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 1
M1 - 34
ER -
