title: Incidence and risk factors for serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors: a report from the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety.
abstract: OBJECTIVE
  To compare tumor necrosis factor-α (TNF-α) inhibitors to nonbiological disease-modifying antirheumatic drugs (DMARD) for the risk of serious infection in Japanese patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Serious infections occurring within the first year of the observation period were examined using the records for patients recruited to the Registry of Japanese Rheumatoid Arthritis Patients for Longterm Safety (REAL), a hospital-based prospective cohort of patients with RA. The analysis included 1144 patients, 646 of whom were treated with either infliximab or etanercept [exposed group: 592.4 patient-years (PY)]. The remaining 498 patients received nonbiological DMARD with no biologics (unexposed group: 454.7 PY).
  
  
  RESULTS
  In the unexposed group, the incidence rate for all serious adverse events (SAE) was 9.02/100 PY and for serious infections, 2.64/100 PY. In the exposed group, SAE occurred in 16.04/100 PY and serious infections in 6.42/100 PY. The crude incidence rate ratio comparing serious infections in the exposed group with the unexposed group was 2.43 (95% CI 1.27-4.65), a significant increase. A multivariate analysis revealed that the use of TNF inhibitors is a significant independent risk factor for serious infection (relative risk 2.37, 95% CI 1.11-5.05, p = 0.026).
  
  
  CONCLUSIONS
  Our study has provided the first epidemiological data on Japanese patients with RA for the safety of TNF inhibitors compared to nonbiological DMARD for up to 1 year of treatment. Anti-TNF therapy was associated with a significantly increased risk for serious infections, compared to treatment with nonbiological DMARD.
authors.affiliation: Department of Pharmacovigilance, Graduate School of Medical and Dental Sciences, and the Clinical Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Komano
authors.forename: Michi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.forename: Ryuji
authors.initials: R
authors.lastname: Koike
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sakai
authors.forename: Hideto
authors.initials: H
authors.lastname: Kameda
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakajima
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takeno
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Naoto
authors.initials: N
authors.lastname: Tamura
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Sawada
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ida
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use*; D015994:Incidence; D007239:Infections / Q000139:chemically induced / Q000453:epidemiology*; D000069285:Infliximab; D007564:Japan / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012042:Registries; D012141:Respiratory Tract Infections / Q000139:chemically induced / Q000453:epidemiology; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept