Tolerability to new COX-2 inhibitors in NSAID-sensitive patients with cutaneous reactions

Background: The safety of new anti-inflammatory drugs in patients intolerant to classic cyclooxygenase (COX) inhibitors with urticaria and angioedema has not been determined. Objectives: To investigate the clinical tolerance to COX-2 inhibitors in patients with cutaneous symptoms attributable to classic nonsteroidal anti-inflammatory drugs (NSAIDs). Methods: Patients with urticaria or angioedema triggered by NSAIDs were challenged with COX-2 inhibitors by the single-blinded, placebo-controlled oral method. Results: One hundred ten NSAID-sensitive patients were submitted to 184 oral challenges with COX-2 inhibitors. Eighty-two patients (74.5%) were cross-reactors and 28 patients (25.4%) were single reactors. Reaction rates for COX-2 inhibitors were 21.3% for nimesulide, 17.3% for meloxicam, 33.3% for celecoxib, and 3.0% for rofecoxib. Conclusions: Some COX-2 inhibitors, such as rofecoxib, are relatively safe in NSAID-sensitive patients with urticaria or angioedema. However, the tolerance profile varies with the drug, which might be related to a differential selectivity of the drug for COX-1 and COX-2. COX-1 inhibition would represent a major mechanism for cutaneous adverse reactions to NSAIDs. Controlled oral provocation with new NSAIDs is useful for the proper management of patients sensitive to classic NSAIDs requiring analgesic and anti-inflammatory treatment.