Mucoprotective drugs can prevent and treat nonsteroidal anti-inflammatory drug-induced small bowel enteropathy: a systematic review and meta-analysis of randomized controlled trials

Background: Small bowel enteropathy (SBE) is a complication of nonsteroidal anti-inflammatory drug (NSAID) therapy occurring in 71% of NSAID users. We aimed to analyse the efficacy and safety of medications to prevent and treat NSAID-induced SBE in randomized controlled trials (RCTs). Methods: This review was registered on PROSPERO (CRD42021223371). We systematically searched four databases until 20 October for comparing mucoprotective (MP), antibiotic and probiotic treatments to placebo, proton-pump inhibitors (PPIs) or histamine-2 (H 2 ) receptor antagonists in NSAID-associated small intestinal injuries. The main outcomes were mucosal integrity, mucosal breaks after treatment, mucosal injury improvement and complete healing of mucosal breaks. Meta-analytical calculations for weighted mean differences (WMDs) and odds ratios (ORs) were performed with the random-effects model and interpreted with 95% confidence intervals (CIs). Results: A total of 18 RCTs were included in the quantitative synthesis. MP medications administered preventively reduced the number of mucosal erosions (WMD = −1.24, CI: −2.15 to −0.34) and lead to a significantly lower chance of developing mucosal breaks after treatment (OR = 0.38, CI: 0.16–0.93). MP therapy was associated with a higher rate of complete healing of mucosal breaks (OR = 5.39, CI: 2.79–10.42). In the qualitative synthesis, there were tendencies for a lower increase in the mean number of mucosal breaks and reddened lesions with prophylactic and a higher decrease in mucosal breaks with therapeutic MP drug administration. Conclusion: MP treatment administered with NSAIDs can prevent and reduce small intestinal mucosal lesions.