Present issues and measures for NSAID-induced small intestinal damage

Abstract

    Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the drugs most frequently used for osteoarthritis and rheumatoid arthritis (RA). It has become a major problem that NSAIDs damage the mucosa of the upper gastrointestinal tract and eventually cause gastric and duodenal ulcer. Moreover, recent studies using video capsule endoscopy and balloon-assisted enteroscopy have clarified that NSAIDs frequently damage the mucosa of small intestine. Although selective COX-2 inhibitors prevent NSAID-induced small intestinal damage in short-term use, it has been shown that the preventive effect is eliminated in long-term use. The use of disease-modifying anti-rheumatic drugs with NSAIDs is considered to aggravate the small intestinal damage. On the other hand, it has been proven that RA patients who receive anti-TNF-α therapy have less severe NSAID-induced small intestinal damage than those who does not receive the therapy. It is clinically significant that proton pump inhibitors (PPIs) cannot protect the small intestine from NSAIDs as hydrochloric acid is not produced in the small intestine. Moreover, some studies have raised the possibility that PPIs might exacerbate the small intestinal damage. Although mucoprotective drug and prostaglandin analogue are expected to be effective for NSAID-induced small intestinal damage at the present, we consider that anti-TNF-α therapy, probiotics, and colchicine could be new candidates for therapeutic agents for the damage. Thus, therapeutic strategies for NSAID-induced gastrointestinal damage need to be established based on these new findings.