title: Initiation of tumor necrosis factor α antagonists and risk of fractures in patients with selected rheumatic and autoimmune diseases.
abstract: OBJECTIVE
  We tested the hypothesis that initiation of tumor necrosis factor α (TNFα) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases.
  
  
  METHODS
  Using 4 large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and a combined group: psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparators.
  
  
  RESULTS
  We identified 9,020, 2,014, and 2,663 new PS-matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD, and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR 1.17, 95% CI 0.91-1.51; HR 1.49, 95% CI 0.72-3.11; and HR 0.92, 95% CI 0.47-1.82 for RA, IBD, and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dosage of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR 1.54, 95% CI 1.03-2.30).
  
  
  CONCLUSIONS
  The risk of fractures did not differ between initiators of a biologic agent and a nonbiologic comparator for any disease studied. Among RA patients, use of >10 mg/day of prednisone equivalents at baseline increased the fracture risk.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Vivian K
authors.initials: VK
authors.lastname: Kawai
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Arbogast
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Delzell
authors.forename: Lang
authors.initials: L
authors.lastname: Chen
authors.forename: Rita
authors.initials: R
authors.lastname: Ouellet-Hellstrom
authors.forename: Lisa
authors.initials: L
authors.lastname: Herrinton
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Edward F
authors.initials: EF
authors.lastname: Mitchell
authors.forename: C Michael
authors.initials: CM
authors.lastname: Stein
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control*; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000009:adverse effects; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012216:Rheumatic Diseases / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D018570:Risk Assessment; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014481:United States
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone