title: Heart failure among younger rheumatoid arthritis and Crohn's patients exposed to TNF-alpha antagonists.
abstract: OBJECTIVE
  New onset heart failure (HF) has been associated with the use of TNF-alpha antagonists etanercept and infliximab based upon spontaneous adverse event reports. HF clinical trials of these agents were stopped early due to futility or worsening of existing HF. A potential association between etanercept and infliximab and new onset HF has been studied minimally at a population level.
  
  
  METHODS
  Using administrative claims from a large U.S. health care organization, we identified rheumatoid arthritis (RA) and Crohn's disease (CD) patients receiving infliximab or etanercept (exposed), and comparator cohorts of RA and CD patients receiving non-biologic immunosuppressives (unexposed). We studied adults < 50 years to reduce potential confounding related to common age-related comorbidities. Based on abstracted medical records of suspected HF cases, a physician panel adjudicated cases as definite, possible or no HF.
  
  
  RESULTS
  Among 4018 RA and CD patients with mean duration follow-up of 18 months, 9 of 33 suspected HF cases (identified using claims data) were adjudicated as definite (n = 5) or possible (n = 4) HF. The relative risk of HF among TNF-alpha antagonist-treated RA and CD patients was 4.3 and 1.2, respectively (P = NS for both). The absolute difference in cumulative incidence of HF among infliximab or etanercept-exposed compared to unexposed patients was 3.4 and 0.3 cases per 1000 persons for RA and CD (P = NS), respectively, yielding a number needed to harm of 294 for RA and 3333 for CD.
  
  
  CONCLUSIONS
  We found only a small number of presumed HF cases (n = 9, or 0.2%) in a large population of relatively young RA and CD patients. Although there was an increased relative risk of incident, HF that was not statistically significant among those exposed to TNF-alpha antagonists compared to those unexposed, larger cohorts are needed to provide more precise risk estimates and permit adjustment for potential confounding.
authors.affiliation: Center for Education and Research on Therapeutics of Musculoskeletal Disorders, The University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Curtis
authors.forename: J M
authors.initials: JM
authors.lastname: Kramer
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.forename: K G
authors.initials: KG
authors.lastname: Saag
authors.forename: N
authors.initials: N
authors.lastname: Patkar
authors.forename: D
authors.initials: D
authors.lastname: Shatin
authors.forename: M
authors.initials: M
authors.lastname: Burgess
authors.forename: A
authors.initials: A
authors.lastname: Xie
authors.forename: M M
authors.initials: MM
authors.lastname: Braun
mesh_terms: D000328:Adult; 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; D003424:Crohn Disease / Q000188:drug therapy*; D000068800:Etanercept; D005260:Female; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
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