The Impact of Recent Data on Our Understanding of the Roles of COX-1 and COX-2 in Gastrointestinal Pathophysiology

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs in the world. In general, these agents have comparable efficacy and are well tolerated, although their use may be limited by their gastrointestinal (GI) tolerability. After the discovery of cyclo-oxygenase (COX)-1 and COX-2 isoforms, COX-1 was postulated to play a role in gastroprotection and COX-2 a role in inflammation and, as known, selective COX-2 inhibitors were developed in an attempt to reduce gastrointestinal toxicity while maintaining therapeutic efficacy. However, recent research challenges the common thinking beyond COX inhibition and related GI adverse reactions showing that GI tolerability might be the result of a combination of COX-dependent mechanisms and the so-called topical effects which NSAIDs - especially those with acid pK - may exert on the GI mucosa. GI tolerability is even more important in the rheumatology patient with concomitant co-morbidities, such as inflammatory bowel disease (IBD), for which the use of NSAIDs is controversial. Results from clinical studies in these patient groups show that NSAIDs such as nimesulide, with its preferential inhibitory activity on the COX-2 isoform and the lack of a topical effect, do not influence the evolution of IBD in patients requiring NSAID treatment for concomitant arthritic complaints. These results further reinforce the GI safety profile of nimesulide in comparison with other NSAIDs, even in particular circumstances, for example in patients with IBD in whom treatment with a NSAID is indicated.