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COX-2 Inhibitors: What Is Their Role?

Two selective inhibitors of cyclooxygenase-2 (COX-2) -- celecoxib (Celebrex) and rofecoxib (Vioxx) -- were FDA approved and marketed relentlessly in 1999. Their main attraction is a potential for fewer gastrointestinal side effects than traditional nonsteroidal anti-inflammatory drugs, which inhibit both gastroprotective COX-1 and proinflammatory COX-2.

One randomized trial compared the effects of rofecoxib and ibuprofen on the gastroduodenal mucosa of osteoarthritis patients (JW Nov 1, p. 165, accession number 991015001, and Gastroenterology Oct; 117:776). On endoscopic examination, rofecoxib was associated with about the same ulcer rate as placebo: 20 percent to 30 percent of that seen with ibuprofen. Clinically apparent complications were similar in all groups. In a pooled analysis of 8 randomized trials, NSAID treatment resulted in about twice the rate of complicated ulcers as rofecoxib (2.6 vs. 1.3 events per 100 patient-years), though both caused about the same rate of dyspepsia. Finally, in a multicenter trial involving 1149 patients with rheumatoid arthritis (JW 2000 Jan 1, p. 1, accession number 991210001, and JAMA Nov 24; 282:1929, 1921), there was no difference in the rate of GI symptoms with celecoxib or naproxen, but endoscopic ulcers were significantly more common in the naproxen group (26 percent vs. 5 percent).

How do the efficacies of COX-2 inhibitors and traditional NSAIDs compare? In the RA trial noted above, and in a randomized trial of osteoarthritis patients (JW Dec 15, p. 192, accession number 991203004, and Mayo Clin Proc Nov; 74:1095), celecoxib and naproxen yielded similar improvements in arthritic signs and symptoms. In yet another study, rofecoxib and naproxen relieved the pain of dysmenorrhea similarly (JW Nov 15, p. 179, accession number 991029006, and Obstet Gynecol Oct; 94:504).

COX-2 inhibitors eventually may prove useful in areas beyond arthritis and pain. For example, a prospective study of colorectal cancer patients explored the relation between COX-2 expression in tumor cells and overall survival, and found that the more intensely the tumor cells stained for COX-2, the worse the prognosis (JW Nov 1, p. 165, accession number 991012002, and JAMA Oct 6; 282:1254). This finding lends biochemical support to the observation that increased NSAID use is associated with a reduced incidence of colorectal tumors.

Although COX-2 inhibitors are associated with a lower risk for endoscopic GI injury than other NSAIDS, the clinical importance of this difference is questionable. Thus, the precise role of these expensive drugs in clinical practice remains uncertain.

— KI Marton

Published in Journal Watch General Medicine December 31, 1999