A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan

Abstract

Objective. To compare the incidence and risk factors of serious adverse events (SAEs) in rheumatoid arthritis (RA) patients treated with etanercept (ETN) or adalimumab (ADA) between Korean and Japanese registries.

Methods. We recruited 416 RA patients [505.2 patient-years (PYs)] who started ETN or ADA from Korean registry and 537 RA patients (762.0 PY) from Japanese registry. The patient background, incidence rate (IR) of SAE in 2 years, and risk factors for SAEs were compared.

Results. Korean patients were younger and used more nonbiologic DMARDs, higher doses of methotrexate, and lower doses of prednisolone (PSL). The IR of SAEs (/100 PY) was higher in the Japanese registry compared to the Korean [13.65 vs. 6.73]. In both registries, infection was the most frequently reported SAE. The only significant risk factor for SAEs in Korean registry was age by decade [1.45]. In Japanese registry, age by decade [1.54], previous use of nonbiologic DMARDs ≥ 4 [1.93], and concomitant use of oral PSL ≥ 5 mg/day [2.20] were identified as risk factors for SAEs.

Conclusions. The IR of SAE in Japan, especially infection, was higher than that of Korea, which was attributed to the difference of demographic and clinical characteristics of RA patients and treatment profiles.

Keywords:

• Epidemiology
• Registry
• Rheumatoid arthritis
• Safety

Acknowledgments

The investigators of the REAL study group and their affiliates who contributed to this work were: Yukiko Komano, Michi Tanaka (Tokyo Medical and Dental University); Koichi Amano (Saitama Medical Center); Shintaro Hirata, Kazuyoshi Saito (University of Occupational and Environmental Health); Yujirou Kon, Tatsuya Atsumi (Hokkaido University); Mitsuhiro Takeno, Yoshiaki Ishigatsubo (Yokohama City University); Taichi Hayashi, Takayuki Sumida (University of Tsukuba); Yukitaka Ueki (Sasebo Chuo Hospital); Takahiko Sugihara (Tokyo Metropolitan Geriatric Hospital); Futoshi Hagiwara, ShigetoTohma (Sagamihara National Hospital); Kazuya Michishita, Kazuhiko Yamamoto (The University of Tokyo); Akira Hashiramoto, Syunichi Shiozawa (Kobe University); Takao Fujii, Tsuneyo Mimori (Kyoto University); Hiroaki Dobashi (Kagawa University); Akitomo Okada, Hiroaki Ida, Katsumi Eguchi, Astushi Kawakami (Nagasaki University); Naoto Tamura, Yoshinari Takasaki (JuntendoUniversity); Hideto Kameda, Yuko Kaneko, Tsutomu Takeuchi (Keio University);Sae Ochi (Tokyo Metropolitan Bokutoh Hospital); Kiyoshi Migita (National Hospital Organization Nagasaki Medical Center); Yasushi Miura (Kobe University); Kenji Nagasaka (Ome Municipal General Hospital); Ayako Nakajima, Hisashi Yamanaka (Tokyo Women's Medical University); Tetsuji Sawada (Tokyo Medical University Hospital). We appreciate Ms. Marie Yajima (Tokyo Medical and Dental University) for her contributions to the maintenance of the REAL database.

Tokyo Kyosai Hospital and Yokohama City Minato Red Cross Hospital are also members of the REAL study group, but was not involved in the present study. We sincerely thank all the rheumatologists and others caring for RA patients enrolled in the REAL registry.

Funding

This work was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (Ministry of Education, Science and Technology) (NRF357-2011-1-E00037). This work was supported by a grant-in-aid from the Ministry of Health, Labor and Welfare, Japan (H23-meneki-sitei-016 and H19-meneki-ippan-009 to N. Miyasaka, H22-meneki-ippann-001 to M. Harigai) and by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (#20390158 to M. Harigai, #19590530 to R. Koike, and #50277141 to M. Tanaka). This work was also supported by grants for pharmacovigilance research on biologics from Abbott Laboratories, Bristol-Myers Japan, Eisai Co. Ltd., Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., and Pfizer Japan Inc. (to M. Harigai), and by a grant from the Japanese Ministry of Education, GCOE Program, “International Research Center for Molecular Science in Tooth and Bone Diseases” (to N. Miyasaka)

Conflict of interests

TN has received research grant from Eisai Co., Ltd.

YT has received consulting fees, speaking fees, and/or honoraria from Mitsubishi Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Takeda Pharmaceutical Co. Ltd., Astellas Pharma Inc., and Abbott Japan Co., Ltd. and has received research grant support from Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Abbott Japan Co., Ltd., and Eisai Co., Ltd.

NM has received research grants from Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Dainihon Sumitomo Pharma Co. Ltd., Daiichi-Sankyo Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Co., Novartis Pharma K.K., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd and received Consulting fee or honorarium from Abbott Japan Co., Ltd., Bristol Myers Squibb, Janssen Pharmaceutical KK, and Otsuka Pharmaceutical Co. Ltd.

DY has received consulting and speaking fee from Celtrion.

SCB has received research grants from Abbott Ltd., Bristol Myers Squibb Pharmaceutical Ltd., Eisai Inc., GlaxoSmithKline Ltd., MSD Ltd. and Pfizer Inc.

MH has received research grants from Abbott Japan Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Co., Ltd.