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

Abstract

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 (H₂) 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.

Keywords: NSAIDs; capsule endoscopy; enteropathy; meta-analysis; small bowel; systematic review.

Figure 1.

PRISMA flow diagram of the screening and selection process. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Figure 2.

Forest plot representing that preventive mucoprotective agents are associated with fewer mucosal erosions compared with control. CI, confidential interval, PGIA, prostaglandin increasing agent.

Figure 3.

Forest plot of studies representing that preventive treatment with mucoprotective agents is associated with a reduced risk of mucosal breaks after treatment compared with control, but not for the PGIA subgroup. CI, confidential interval, PGIA, prostaglandin increasing agent.

Figure 4.

Forest plot of studies representing that treatment with mucoprotective agents is associated with a higher chance for complete healing of mucosal breaks compared with control. CI, confidential interval, PGIA, prostaglandin increasing agent.