Comparison of COX-2 Selective and Traditional NSAIDs on Experimental Gastric Ulcer Healing in Humans

Abstract

Background: Nonsteroidal anti-inflammatory drugs impair gastrointestinal ulcers healing. This study evaluated the role of cyclooxygenase isozymes COX- 1 and COX-2 in the healing of acute gastric ulcers in humans. Methods: This was an open-label, endoscopist-blind, parallel-group study, age and sex matched at baseline in normal volunteers. At endoscopy, we took four large jumbo forceps gastric mucosal biopsies (2 from each of the antrum and corpus). Subjects received celecoxib 200mg bid), naproxen 500mg bid), nabumetone 1000mg bid or placebo until end of study. Endoscopies were performed after 5 days and every 3 days until complete re-epithelialization of all lesions or 30 days. Survival analysis was used to compare time-to-healing defined as the day with complete re-epithelialization of all ulcers. Results: Fifty-two subjects completed the study, each received four biopsyinduced gastric ulcers (204 total ulcers; the majority included the muscularis mucosa). The mean time-to-healing was 9.4 ± 0.4 days with placebo, 10.5 ± 0.4 with celecoxib, 11.1 ± 0.6 with naproxen, and 12.3 ± 0.9 with nabumetone. The time to healing of each ulcer or all ulcers was significantly delayed compared to placebo with naproxen (p=0.01) and nabumetone (p=0.002) but not with celecoxib (p=0.07). Conclusion: The COX-1 preferential inhibitor naproxen and the balanced COX-1/COX-2 inhibitor nabumetone significantly delayed the healing of ulcers. With the COX-2 specific inhibitor celecoxib, healing was delayed but not significantly. Synthesis of COX-1 derived prostaglandins appears to be important in the healing of gastric ulcers in humans.