Heterogeneity in protocols and outcomes to study the effect of renin-angiotensin system blockers in inflammatory bowel disease: A systematic review.

Background: The renin-angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion.

Objectives: We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in IBD.

Methods: This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO-CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES's risk of bias tools for animal studies.

Results: Thirty-five pre-clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies.

Conclusion: Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes.