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-r heumatic drugs. The frequency and severity of their side effects on the gas trointestinal tract is a major health issue. A part of the toxicity of conv entional non-steroidal anti-inflammatory drugs is due to their "topical" ef fect as well as their inhibition of cyclo-oxygenase-1. It has been suggeste d that the emergence of highly specific and selective cyclo-oxygenase-2 inh ibitors will lead to significant decrease in gastrointestinal damage while maintaining or even improving therapeutic efficacy. Here I review the stren gth and weaknesses of conventional methods for assessing gastric and small intestinal safety of non-steroidal anti-inflammatory drugs. The available s afety data for a range of cyclo-oxygenase-2 selective agents (meloxicam, ni mesulide, celecoxib and vioxx) is reviewed. Short term endoscopy studies sh ow minimal damage with these drugs and there is some data to suggest, at le ast for celecoxib and vioxx, that long term ingestion is not associated wit h significant gastric damage. Serious outcome studies are not available, bu t there is a suspicion that meloxicam may not be devoid of toxicity. Short term studies assessing intestinal permeability, which appear to give predic tive information on the longer term small intestinal tolerability, show tha t meloxicam increases intestinal permeability while neither nimesulide or v ioxx do so. Furthermore nimesulide does not cause non-steroidal anti-inflam matory drug-enteropathy when taken short term. So far the more selective cy clo-oxygenase-2 inhibitors are living up to their promise.