Upper Gastroduodenal Ulceration in Arthritis Patients Treated with Celecoxib

Nonsteroidal antiinflammatory drugs (NSAIDs) are as-sociated with gastrointestinal (GI) problems, notably dyspepsia and bleeding. A large prospective trial1 with more than 8000 patients with rheumatoid arthritis (RA) taking NSAIDs has shown that the rate of serious GI com-plications is 1.5 % per year. Patients with no risk factors have a risk of 0.4%, rising to 5 % in high-risk patients. Given the size of the NSAID market, these serious GI ad-verse effects have become a major healthcare problem. In the UK, estimates2 suggest that the cost to the National Health Service of GI adverse effects related to NSAIDs is £251 million (British pounds) each year. Attempts to avoid these complications have included the concomitant admin-istration of acid-suppressant therapy or prostaglandin ana-logs. Traditional NSAIDs are nonselective cyclooxygenase (COX) inhibitors, reducing the actions of both COX-1 and COX-2 isoforms of the enzyme. The development of COX-2–specific inhibitors as potentially less harmful NSAIDs is based on the fact that COX-1 predominates in the stomach, yielding protective prostaglandins, while COX-2 is induced in inflammation, giving rise to pain, swelling, and stiffness.3 Results from clinical trials suggest that if COX-2–specific inhibitors have any benefit over nonselective traditional NSAIDs, it is not through increased efficacy but rathe