title: Safety of high-dose rofecoxib in patients with aspirin-exacerbated respiratory disease.
abstract: BACKGROUND
  Aspirin-exacerbated respiratory disease (AERD) is characterized by progressive sinusitis, nasal polyposis, and asthma that begins and continues in the absence of exposure to aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs). Cross-sensitivity to all NSAIDs that inhibit cyclooxygenase-1 (COX-1) occurs in these individuals. Reactions to aspirin and NSAIDs in patients with AERD are largely due to inhibition of COX-1. Despite accumulating data on the safety of COX-2 selective inhibitors in AERD, concern still remains that high doses of a COX-2 inhibitor may be sufficient to induce a cross-reaction.
  
  
  OBJECTIVE
  To determine whether high-dose rofecoxib cross-reacts in patients with AERD and asthma.
  
  
  METHODS
  Sixty asthmatic patients underwent blinded placebo-controlled oral challenges with 50 mg of rofecoxib. Aspirin sensitivity was subsequently confirmed in all patients with the use of single-blinded aspirin challenges.
  
  
  RESULTS
  None of the 60 patients experienced any symptoms, changes in nasal examination results, or declines in lung function during rofecoxib challenge. All 60 patients experienced respiratory reactions to aspirin challenge, with a mean provoking dose of 57 mg. The exact 1-sided 95% confidence interval for the underlying probability of 50 mg of rofecoxib inducing respiratory cross-reactions in patients with AERD is 0 to 0.05, or 0% to 5%.
  
  
  CONCLUSIONS
  These results confirm the lack of cross-reactivity of aspirin and the highly selective COX-2 inhibitors in AERD. We suggest that it is time for the labeling of highly selective COX-2 inhibitors to reflect these data and for the warning that patients with AERD in particular and asthmatic patients in general avoid selective COX-2 inhibitors to be removed.
authors.affiliation: Scripps Clinic Medical Group, The Scripps Research Institute, La Jolla, California 92037, USA. kwoessner@scrippsclinic.com
authors.forename: Katharine M
authors.initials: KM
authors.lastname: Woessner
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Simon
authors.forename: Donald D
authors.initials: DD
authors.lastname: Stevenson
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology; D003429:Cross Reactions; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007783:Lactones / Q000009:adverse effects*; D012130:Respiratory Hypersensitivity / Q000139:chemically induced* / Q000188:drug therapy / Q000276:immunology; D013450:Sulfones; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D001241:Aspirin