title: Risk of mortality, fatal infection, and fatal malignancy related to use of anti-tumor necrosis factor-α biologics by rheumatoid arthritis patients.
abstract: OBJECTIVE
  To estimate rates of all-cause mortality, fatal infection, and fatal malignancy in rheumatoid arthritis (RA) patients treated with anti-tumor necrosis factor-α (anti-TNF) biologics.
  
  
  METHODS
  A retrospective cohort study of RA patients initiating therapy with adalimumab, etanercept, or infliximab from January 2000 to December 2008 was conducted using an administrative database of a large health care insurer. Patients were followed for the occurrence of fatal events, which were identified using the National Death Index database. Overall and anti-TNF biologic-stratified incidence rates per 1000 person-years were calculated. Primary analyses were time-on-drug based on current anti-TNF biologic exposure on the outcome date for fatal infection and intent-to-treat based on the anti-TNF biologic initiated at cohort entry for fatal malignancy.
  
  
  RESULTS
  Seven thousand seven hundred thirty-four patients initiated an anti-TNF biologic with 13,296 person-years of observation. Seventy-one deaths were identified, including 12 fatal infections and 21 fatal malignancies. The all-cause mortality rate was 5.34 per 1000 person-years. Incidence rates for fatal infection were similar among anti-TNF biologic current exposure groups (0.78 to 0.88 per 1000 person-years). Incidence rates for fatal malignancy were similar among anti-TNF biologic initiator groups (1.24 to 1.84 per 1000 person-years).
  
  
  CONCLUSIONS
  The all-cause mortality rate in RA patients treated with anti-TNF biologics was lower than in previous studies in similar non-US populations, but comparable to mortality rates in the US general population. Fatal infection and fatal malignancy rates were similar across anti-TNF biologic groups. Further studies, designed to detect risk differences associated with anti-TNF biologic use and baseline risk factors, would provide additional information.
authors: Epidemiology Division, OptumInsight, Ann Arbor, MI 48108, USA. veena.thyagarajan@optum.com
authors: Veena
authors: V
authors: Thyagarajan
authors: Heather
authors: H
authors: Norman
authors: Kimberly A
authors: KA
authors: Alexander
authors: Pavel
authors: P
authors: Napalkov
authors: Cheryl
authors: C
authors: Enger
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D001424:Bacterial Infections / Q000209:etiology / Q000401:mortality*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology / Q000401:mortality*; D018124:Receptors, Tumor Necrosis Factor; D012189:Retrospective Studies; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept