title: Rates of serious infections, opportunistic infections, inflammatory bowel disease, and malignancies in subjects receiving etanercept vs. controls from clinical trials in ankylosing spondylitis: a pooled analysis.
abstract: OBJECTIVE
  Therapies involving anti-tumour necrosis factor are associated with increased risk of serious infections, opportunistic infections, and some types of malignancies in subjects with rheumatic diseases. However, limited data have been collected for subjects with ankylosing spondylitis (AS). The aim of this retrospective analysis of all sponsor-conducted trials was to examine the rates of serious infections, inflammatory bowel disease (IBD), malignancies, and non-malignant skin cancers during treatment in subjects with AS.
  
  
  METHODS
  Data from five randomized controlled trials (one sulfasalazine-controlled, four placebo-controlled) and four open-label studies evaluating etanercept were pooled for analyses. All randomized subjects who received at least one dose of treatment were included in the study.
  
  
  RESULTS
  Analyses included 1323 subjects (> 1500 subject-years of treatment). Rate ratios of serious infections and IBD events for etanercept vs. placebo/sulfasalazine during the double-blind studies were 2.19 [95% confidence interval (CI) 0.22-107.79] and 1.09 (95% CI 0.06-64.56), respectively. There were no reports of opportunistic infections. Using the Surveillance, Epidemiology and End Results database, the standardized incidence ratio for malignancies was 1.47 (95% CI 0.54-3.21).
  
  
  CONCLUSIONS
  These data suggest that etanercept is well tolerated in subjects with AS. Despite the large number of patients, the 95% CI data all cross 1.0, limiting possible conclusions. No new safety signals were observed.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre , Leiden , The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van der Heijde
authors.forename: D
authors.initials: D
authors.lastname: Zack
authors.forename: J
authors.initials: J
authors.lastname: Wajdula
authors.forename: S
authors.initials: S
authors.lastname: Sridharan
authors.forename: A S
authors.initials: AS
authors.lastname: Koenig
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007239:Infections / Q000139:chemically induced / Q000453:epidemiology*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D009894:Opportunistic Infections / Q000139:chemically induced / Q000453:epidemiology; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept