The safety of celecoxib in patients with aspirin‐sensitive asthma

Abstract

Objective. To determine whether celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, cross-reacts in patients with aspirin-exacerbated respiratory disease (AERD) with asthma.Methods. Sixty patients with asthma underwent double-blinded, placebo-controlled oral challenges with celecoxib (100 mg, 200 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, sensitivity to acetylsalicylic acid (ASA) was proven in all patients with the use of single-blinded ASA challenges.Results. None of the 60 patients experienced any symptoms, changes in nasal examinations, or declines in forced expiratory volume in 1 second during the celecoxib challenges. All 60 patients experienced oculonasal and/or asthmatic reactions to ASA, with a mean provoking dose of 69 mg. The exact 1-sided confidence interval for the probability of celecoxib inducing crossreactions in AERD patients was calculated to be between 0% and 5%.Conclusion. Cross-reactivity between ASA and celecoxib does not occur in patients with AERD. These results do not preclude the possibility of other types of immune reactions occurring with celecoxib after prior exposure. Our results add to the growing body of evidence that inhibition of COX-1 is a critical initiating event in the precipitation of respiratory reactions in AERD patients following ingestion of nonsteroidal antiinflammatory drugs.

Aspirin-Exacerbated Respiratory Disease: Prevalence, Diagnosis, Treatment, and Considerations for the Future

“…Reactions to acetaminophen are unusual but can occur. [28][29][30][31][32] The dogma indicates that reactions in patients with AERD are triggered by the inhibition of COX-1, which is not a biologic activity of nonaspirin salicylates and, as such, dietary salicylates are generally not thought to trigger reactions. However, results of recent research showed that a low-salicylate diet perhaps leads to a reduction in symptoms in some patients with AERD.…”

Prostaglandin E2deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes

“…Impaired EP receptor input compromises control of TP receptor signaling by PKA (28), increasing the adherence of platelets to granulocytes, inducing endothelial ICAM-1 (28), activating 5-LO, and enabling platelet-adherent leukocytes to mediate LT generation (9). The residual local PGE 2 derives principally from COX-1, which may explain why only COX-1 active drugs provoke clinical reactions (6) and why COX-2-selective drugs are well tolerated by these patients (20). The MC activation typical of clinical reactions (50,63,64) may be due to the agonistic effects of cysLTs derived from intrapulmonary platelet-granulocyte complexes when residual PGE 2 is depleted.…”

“…The dependency on COX products to maintain homeostasis over 5-LO activity is a unique feature of AERD. Remarkably, subjects with AERD can tolerate selective antagonists of COX-2 (20), suggesting that the homeostatic prostaglandins derive principally from COX-1.…”

Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation

“…Reports suggest that COX-2 selective NSAIDs may be safer than nonselective NSAIDs in aspirin-sensitive asthmatics. 72 NSAIDs, including COX-2 selective drugs, may also exacerbate inflammatory bowel diseases.…”