title: Initiation of rheumatoid arthritis treatments and the risk of serious infections.
abstract: OBJECTIVE
  In clinical trials of RA patients on traditional DMARDs, the addition of TNF-alpha antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results.
  
  
  METHODS
  We estimated hospitalization rates for infections following initiation of TNF-alpha antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995-2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002-05 and first episodes of use and explored effects of unmeasured confounders.
  
  
  RESULTS
  We identified 28 906 new episodes of medication use, including TNF-alpha antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-alpha antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results.
  
  
  CONCLUSIONS
  Compared with initiation of MTX alone, initiation of TNF-alpha antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dose-dependent increase in the risk of these infections.
authors.affiliation: Department of Preventive Medicine, Center for Education and Research on Therapeutics, Vanderbilt University School of Medicine, 1500 21st Avenue Suite 2600, The Village at Vanderbilt, Nashville, TN 37232-2637, USA. carlos.grijalva@vanderbilt.edu
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.forename: Lisa
authors.initials: L
authors.lastname: Kaltenbach
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Arbogast
authors.forename: Edward F
authors.initials: EF
authors.lastname: Mitchel
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D009894:Opportunistic Infections / Q000453:epidemiology* / Q000276:immunology; D011014:Pneumonia / Q000453:epidemiology / Q000276:immunology; D018570:Risk Assessment / Q000379:methods; D013714:Tennessee / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D018501:Antirheumatic Agents; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate