title: Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases.
abstract: BACKGROUND
  Although tumor necrosis factor (TNF)-α antagonists are increasingly used in place of nonbiologic comparator medications, their safety profile remains incomplete.
  
  
  OBJECTIVE
  To determine whether initiation of TNF-α antagonists compared with nonbiologic comparators is associated with an increased risk of serious infections requiring hospitalization.
  
  
  METHODS
  Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998-2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis, or ankylosing spondylitis (psoriasis and spondyloarthropathies) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid, and national Medicaid/Medicare. TNF-α antagonists and nonbiologic regimens were compared in disease-specific propensity score (PS)-matched cohorts using Cox regression models with nonbiologics as the reference. Baseline glucocorticoid use was evaluated as a separate covariate.
  
  
  METHODS
  Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or nonbiologic regimens.
  
  
  RESULTS
  Study cohorts included 10,484 RA, 2323 IBD, and 3215 psoriasis and spondyloarthropathies matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1172 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among patients with RA, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR], 1.05 [95% CI, 0.91-1.21]). Among patients with IBD, rates were 10.91 (TNF-α antagonists) and 9.60 (comparator) per 100 person-years (aHR, 1.10 [95% CI, 0.83-1.46]). Among patients with psoriasis and spondyloarthropathies, rates were 5.41 (TNF-α antagonists) and 5.37 (comparator) per 100 person-years (aHR, 1.05 [95% CI, 0.76-1.45]). Among patients with RA, infliximab was associated with a significant increase in serious infections compared with etanercept (aHR, 1.26 [95% CI, 1.07-1.47]) and adalimumab (aHR, 1.23 [95% CI, 1.02-1.48]). Baseline glucocorticoid use was associated with a dose-dependent increase in infections.
  
  
  CONCLUSIONS
  Among patients with autoimmune diseases, compared with treatment with nonbiologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.
authors: Division of Pharmacoepidemiology, Department of Preventive Medicine, Vanderbilt University School of Medicine, 1500 21st Ave S, Ste 2600, The Village at Vanderbilt, Nashville, TN 37212, USA. carlos.grijalva@vanderbilt.edu
authors: Carlos G
authors: CG
authors: Grijalva
authors: Lang
authors: L
authors: Chen
authors: Elizabeth
authors: E
authors: Delzell
authors: John W
authors: JW
authors: Baddley
authors: Timothy
authors: T
authors: Beukelman
authors: Kevin L
authors: KL
authors: Winthrop
authors: Marie R
authors: MR
authors: Griffin
authors: Lisa J
authors: LJ
authors: Herrinton
authors: Liyan
authors: L
authors: Liu
authors: Rita
authors: R
authors: Ouellet-Hellstrom
authors: Nivedita M
authors: NM
authors: Patkar
authors: Daniel H
authors: DH
authors: Solomon
authors: James D
authors: JD
authors: Lewis
authors: Fenglong
authors: F
authors: Xie
authors: Kenneth G
authors: KG
authors: Saag
authors: Jeffrey R
authors: JR
authors: Curtis
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015331:Cohort Studies; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D007239:Infections / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012306:Risk; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology
chemical_list: D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha