Lack of cross-reactivity between rofecoxib and aspirin in aspirin-sensitive patients with asthma

Background: Patients with aspirin-sensitive respiratory disease experience cross-reactions to all nonsteroidal anti-inflammatory drugs, which inhibit cyclooxygenase enzymes. With the introduction of antiarthritis drugs, which selectively inhibit cyclooxygenase-2, questions are raised as to whether c rossreactivity occurs between aspirin and these new cyclooxygenase-2 inhibi tors. Objective: The goal of this study was to determine whether rofecoxib cross- reacts in aspirin-sensitive patients with asthma. Methods: Sixty patients with asthma underwent double-blinded, placebo-contr olled oral challenges with rofecoxib (12.5 mg, 25 mg, and 2 placebos) over 48 hours in our General Clinical Research Center. The next day, aspirin sen sitivity was proven in each of the 60 patients through use of single-blinde d oral aspirin challenges. Results: None of the 60 patients experienced any symptoms, changes in nasal examination findings, or declines in FEV1 values during their challenges w ith rofecoxib. All 60 patients experienced typical naso-ocular and asthmati c reactions to aspirin with a mean provoking dose of 61 mg. The exact 1-sid ed C1 for the probability of rofecoxib inducing cross-reactions in aspirin- sensitive patients with asthma is calculated to be between 0% and 0.05%. Conclusion: Given that none of the 60 patients reacted to rofecoxib and giv en the statistical power of this large sample size, we conclude that cross- reactivity between aspirin and rofecoxib does not occur in patients with as pirin-sensitive respiratory disease. This does not exclude rofecoxib from p articipating in other types of reactions, including immune recognition afte r prior treatment with the drug. From the standpoint of the mechanisms invo lved in aspirin-induced respiratory reactions, this study strongly supports inhibition of cyclooxygenase-1 as the essential initiator of these types o f reactions.