Forthcoming non-steroidal anti-inflammatory drugs: are they really devoid of side effects?

Non-steroidal anti-inflammatory drugs are the most prescribed of the anti-rheumatic drugs. The frequency and severity of their side effects on the gastrointestinal tract is a major health issue. A part of the toxicity of conventional non-steroidal anti-inflammatory drugs is due to their "topical" effect as well as their inhibition of cyclo-oxygenase-1. It has been suggested that the emergence of highly specific and selective cyclo-oxygenase-2 inhibitors will lead to significant decrease in gastrointestinal damage while maintaining or even improving therapeutic efficacy. Here I review the strength and weaknesses of conventional methods for assessing gastric and small intestinal safety of non-steroidal anti-inflammatory drugs. The available safety data for a range of cyclo-oxygenase-2 selective agents (meloxicam, nimesulide, celecoxib and vioxx) is reviewed. Short term endoscopy studies show minimal damage with these drugs and there is some data to suggest, at least for celecoxib and vioxx, that long term ingestion is not associated with significant gastric damage. Serious outcome studies are not available, but there is a suspicion that meloxicam may not be devoid of toxicity. Short term studies assessing intestinal permeability, which appear to give predictive information on the longer term small intestinal tolerability, show that meloxicam increases intestinal permeability while neither nimesulide or vioxx do so. Furthermore nimesulide does not cause non-steroidal anti-inflammatory drug-enteropathy when taken short term. So far the more selective cyclo-oxygenase-2 inhibitors are living up to their promise.