Is everyone certain that there's no description of gastropathy due to celecoxib (Celebrex)?
Here's a letter in the current NEJM on this very issue. OTOH, the new drugs are undoubtedly safer than existing NSAIDS, which cause large numbers (in absolute terms, not relative to use) of deaths each year.
The New England Journal of Medicine -- June 24, 1999 -- Vol. 340, No. 25
Gastropathy Due to Celecoxib, a Cyclooxygenase-2 Inhibitor
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To the Editor:
Celecoxib (Celebrex), a cyclooxygenase (COX)-2-specific nonsteroidal antiinflammatory drug (NSAID), was recently introduced in the U.S. market. COX-2 is induced in inflammation, whereas COX-1 produces protective prostaglandins in the stomach. Because of its specificity for COX-2, celecoxib is less likely to cause gastric injury. A one-week endoscopic study of gastrointestinal mucosal effects in phase 2 trials showed that gastric ulcers developed in 19 percent of the subjects receiving naproxen, whereas no ulcers developed in the subjects receiving celecoxib or placebo. (1) We describe a patient in whom NSAID-induced gastropathy developed while she was taking celecoxib.
A 69-year-old woman presented with abdominal cramps. She was found to have antibodies to Helicobacter pylori and was treated with lansoprazole, amoxicillin, and clarithromycin eight weeks before presentation. She had been treated with tramadol for arthritis; the medication was switched to celecoxib, in doses of 100 mg twice a day, six weeks before presentation. While the patient was taking celecoxib, severe epigastric pain developed. Another two-week course of treatment for H. pylori was given four weeks before presentation. She was referred to us since the epigastric pain persisted. Esophagogastroduodenoscopy revealed severe, erosive gastropathy with multiple petechial hemorrhages and small erosions involving the body and antrum. Histologically, no inflammation was seen in the body, and slight inflammation was seen in the antrum, findings compatible with NSAID-induced gastropathy. H. pylori was not identified. Treatment with celecoxib was discontinued, and the patient was giv!
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en 40 mg of omeprazole by mouth twice a day for a week and then once a day. The burning abdominal pain resolved in a week.
NSAIDs with COX-2 selectivity had antiinflammatory effects in mice only at doses at which they inhibited COX-1. (2) At these doses, they inhibited gastric prostaglandin synthesis and elicited gastric erosions. COX-2 was induced in the stomach after injury, and COX-2 inhibitors impaired the healing of ulcers in mice. (3) This finding implies a role for gastric prostaglandins derived from COX-2 in mucosal resistance to injury. COX-2 was localized in the base of gastric ulcers in rats, which suggests a role for COX-2 in the healing of ulcers. (4) Even though celecoxib was not tested in these studies, the results raise the possibility of gastric mucosal injury with COX-2 inhibitors. This case report indicates that COX-2 inhibitors can cause gastric mucosal damage. The gastropathy was endoscopically and histologically characteristic of NSAID-induced gastropathy. Physicians should be aware of the potential for gastric injury with COX-2 inhibitors.
Suneel Mohammed, M.D.
Dorwyn W. Croom II, M.D.
Grace Health Care System
Morganton, NC 28655
References
1. Simon LS, Lanza FL, Lipsky PE, et al. Preliminary study of the safety and efficacy of SC-58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo-controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis Rheum 1998;41:1591-602.
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2. Wallace JL, Bak A, McKnight W, Asfaha S, Sharkey KA, MacNaughton WK. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity. Gastroenterology 1998;115:101-9.
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3. Mizuno H, Sakamoto C, Matsuda K, et al. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice. Gastroenterology 1997;112:387-97.
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4. Takahashi S, Shigeta J, Inoue H, Tananbe T, Okabe S. Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats. Am J Physiol 1998;275:G1137-G1145. |
