title: Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since implementation in Japan: long-term results from a multicenter observational cohort study.
abstract: This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan.
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550. toshik@med.nagoya-u.ac.jp.
authors: Toshihisa
authors: T
authors: Kojima
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Nobunori
authors: N
authors: Takahashi
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Koji
authors: K
authors: Funahashi
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Shuji
authors: S
authors: Asai
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Kenya
authors: K
authors: Terabe
authors: Department of Orthopedic Surgery, Nagoya Medical Center, Nagoya, Japan.
authors: Atsushi
authors: A
authors: Kaneko
authors: Department of Rheumatology, Toyohashi Municipal Hospital, Toyohashi, Japan.
authors: Yuji
authors: Y
authors: Hirano
authors: Department of Rheumatology, Nagano Red Cross Hospital, Nagano, Japan.
authors: Masatoshi
authors: M
authors: Hayashi
authors: Department of Orthopedic Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan.
authors: Hiroyuki
authors: H
authors: Miyake
authors: Department of Orthopedic Surgery, Anjo Kosei Hospital, Anjo, Japan.
authors: Takeshi
authors: T
authors: Oguchi
authors: Department of Orthopedic Surgery, Nagoya Central Hospital, Nagoya, Japan.
authors: Hideki
authors: H
authors: Takagi
authors: Department of Rheumatology, Toyota Kosei Hospital, Nagoya, Japan.
authors: Yasuhide
authors: Y
authors: Kanayama
authors: Department of Rheumatology, JCHO Tokyo Sinjuku Medical Center, Tokyo, Japan.
authors: Yuichiro
authors: Y
authors: Yabe
authors: Department of Orthopedic Surgery, Kariya-Toyota General Hospital, Kariya, Japan.
authors: Tsuyoshi
authors: T
authors: Watanabe
authors: Department of Orthopedic Surgery, Konan Kosei Hospital, Konan, Japan.
authors: Takayoshi
authors: T
authors: Fujibayashi
authors: Department of Orthopedic Surgery, Shizuoka Kosei Hospital, Shizuoka, Japan.
authors: Tomone
authors: T
authors: Shioura
authors: Ito Orthopedic Clinic, Nagoya, Japan.
authors: Takayasu
authors: T
authors: Ito
authors: Department of Orthopedic Surgery, Handa Municipal Hospital, Handa, Japan.
authors: Yutaka
authors: Y
authors: Yoshioka
authors: Department of Rheumatology, Japanese Red Cross, Nagoya Daiichi Hospital, Nagoya, Japan.
authors: Hisato
authors: H
authors: Ishikawa
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Nobuyuki
authors: N
authors: Asai
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Toki
authors: T
authors: Takemoto
authors: Department of Public Health, Faculty & Graduate School of Medicine, Nagoya City University, Nagoya, Japan.
authors: Masayo
authors: M
authors: Kojima
authors: Department of Orthopedic Surgery & Rheumatology, Nagoya University Hospital, 65 Tsurumai, Showa, Nagoya, Japan, 466-8550.
authors: Naoki
authors: N
authors: Ishiguro
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000628:therapy*; D001691:Biological Therapy / Q000379:methods*; D015331:Cohort Studies; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000069285:Infliximab; D000068879:Adalimumab; C502936:tocilizumab; D000068800:Etanercept
keywords: Adverse event; Biologics; Rheumatoid arthritis; Safety