[Nonsteroidal anti-inflammatory agents in the management of rheumatic disorders]

Nonsteroidal anti-inflammatory drugs (NSAIDs) have become one of the most commonly used drug classes. However, the gastrointestinal adverse effects, including ulcers, perforation and bleeding, constitute a major problem, although the risk of their occurrence appears to vary according to the different classical NSAIDs used. These drugs inhibit the key enzyme in prostaglandin biosynthesis, cyclo-oxygenase or COX. COX exists in 2 isomeric forms, COX-1 and COX-2, which are inhibited to different extents by the classical NSAIDs. COX-1 leads, for example, to the production of prostaglandins that are cytoprotective for the gastric mucosa. COX-2 is inducible in a number of cells by pro-inflammatory stimuli. The selective COX concept predicts that inhibition of COX-1 may result in gastrointestinal adverse effects, whereas inhibition of COX-2 may underlie the anti-inflammatory actions of NSAIDs. These observations have led to the development of new drugs with high inhibitory potency for COX-2 and low potency for COX-1. These selective COX-2 inhibitors appear to be promising in animal models and endoscopic studies in humans. If large clinical and epidemiological studies confirm that (i) selective COX-2 inhibitors are as effective as classical NSAIDs, (ii) the frequency of severe gastrointestinal complications is considerably reduced with these new drugs, and (iii) no unexpected complications of selective COX-2 inhibition are detected, then selective COX-2 inhibitors will prove to be a significant advance in the treatment of patients with rheumatic diseases.