title: Time-dependent increased risk for serious infection from continuous use of tumor necrosis factor antagonists over three years in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate associations between continuous treatments with tumor necrosis factor (TNF) antagonists and risk for developing serious infections (SIs) over 3 years in Japanese patients with rheumatoid arthritis (RA) enrolled in the Registry of Japanese RA Patients for Long-Term Safety (REAL) database.
  
  
  METHODS
  We analyzed 727 RA patients who had started either infliximab or etanercept (the anti-TNF group; 1,480.1 patient-years [PY]) and 571 RA patients who had started conventional nonbiologic disease-modifying antirheumatic drugs (the unexposed group; 1,104.1 PY) at the time of enrollment in the REAL. We assessed the occurrence of SIs within a 3-year observation period, including the period after switching to other TNF antagonists, and all SIs, unlimited to the first one in each patient as reported in other studies, to evaluate the real safety of TNF antagonists in daily practice.
  
  
  RESULTS
  The incidence rate of SIs per 100 PY was 5.54 (95% confidence interval [95% CI] 4.44-6.84) in the anti-TNF group and 2.72 (95% CI 1.87-3.83) in the unexposed group. Poisson regression analysis revealed that the relative risk (RR) of continuous use of TNF antagonists for SIs after adjusting for baseline and time-dependent covariates was significantly elevated both overall (1.97, 95% CI 1.25-3.19) and for the first year (2.40, 95% CI 1.20-5.03), but not for the second and third years combined (1.38, 95% CI 0.80-2.43). The adjusted RR for SIs of etanercept compared to infliximab was not significantly elevated.
  
  
  CONCLUSIONS
  Continuous anti-TNF therapy was significantly associated with increased risks for developing SIs during, but not after, the first year.
authors.affiliation: Tokyo Medical and Dental University, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Sakai
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: Hayato
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Amano
authors.forename: Atsuo
authors.initials: A
authors.lastname: Nakajima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takao
authors.initials: T
authors.lastname: Koike
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ihata
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida
authors.forename: Shigeto
authors.initials: S
authors.lastname: Tohma
authors.forename: Naoto
authors.initials: N
authors.lastname: Tamura
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sugihara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
authors.forename: Noboru
authors.initials: N
authors.lastname: Hagino
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Ueki
authors.forename: Akira
authors.initials: A
authors.lastname: Hashiramoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagasaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Miyasaka
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Harigai
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology*; D015331:Cohort Studies; D003141:Communicable Diseases / Q000139:chemically induced / Q000453:epidemiology*; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects*; D000069285:Infliximab; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept