Safety of Celecoxib vs Other Nonsteroidal Anti-inflammatory Drugs

To the Editor: The results of the Celecoxib Long-term Arthritis Safety Study (CLASS)¹ support the hypothesis that celecoxib alone does not induce anatomical lesions in the gastrointestinal (GI) tract.

However, in the subgroup of patients who were receiving aspirin for cardiovascular disease there was no difference in nonsteroidal anti-inflammatory drug (NSAID)–induced GI complications between celecoxib and aspirin vs conventional ibuprofen or diclofenac and aspirin. Because cyclooxygenase (COX)-1 is responsible for GI integrity under physiological conditions and because COX-2–specific inhibitors alone do not cause anatomical lesions, we would have expected a lower rate of ulcer complications in the group receiving celecoxib and aspirin. As outlined in the accompanying Editorial by Drs Lichtenstein and Wolfe,² a possible explanation for this surprising finding might be a type II error due to the small sample size. However, the small numerical difference observed between the 2 groups suggests that even a statistically significant result in a study with a much larger sample size would translate into questionable clinical benefit. Alternatively, healing of aspirin-induced anatomical lesions, which normally involves COX-2 induction, might be delayed by celecoxib.³ In the CLASS trial, there was no washout period, and many patients were receiving NSAIDs at baseline. Therefore, many of these patients were at risk for asymptomatic NSAID-induced gastropathy at the time they entered the study. Thus, although COX-2–specific inhibitors are not specifically ulcerogenic, they may interfere with repair of NSAID-induced gastropathy.