What is the presumptive therapeutic advantage of COX-2 selective NSAIDs?
The COX-2 inhibitors have been successfully marketed based on the presumption that the main mechanism by which nonselective NSAIDs cause gastrointestinal (GI) ulcers is inhibition of COX-1. Based on this hypothesis, drugs that selectively inhibit COX-2 enzymes will have similar anti-inflammatory activity with less GI toxicity. Short-term randomized clinical trials, in which all patients underwent endoscopy, showed fewer cumulative gastroduodenal erosions and ulcers with the COX-2 inhibitors (9-15%) than with nonselective NSAIDs (41-46%) (2). Regulatory authorities judged this surrogate outcome insufficient to prove that COX-2 selective inhibitors were better than nonselective NSAIDs in terms of the life-threatening complications of NSAIDs: ulcers complicated by GI bleeds, perforations and obstructions. Thus the monographs of celecoxib, rofecoxib (Vioxx®) and meloxicam (Mobicox®) include the same warnings of the risk of GI toxicity as all other NSAIDs. What was the objective of the CLAS
