Efficacy and safety of PPAR agonists in primary biliary cholangitis: a systematic review and meta-analysis.

Abstract

Background: Managing patients with primary biliary cholangitis (PBC) who demonstrate an inadequate response to ursodeoxycholic acid or experience intolerable side effects remains a significant clinical challenge.

Objectives: This study aims to investigate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in the treatment of PBC.

Design: Meta-analysis and systematic review.

Methods: A systematic search of publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was performed. Randomized controlled trials published in English that involved the treatment of PPAR agonists and reported on the levels of alkaline phosphatase (ALP), biochemical response rates, pruritus score, or severe and serious adverse events (AEs) were selected. The primary outcomes assessed were the effects of PPAR agonists on ALP levels and biochemical response rates. Secondary outcomes included the rates of severe or serious AEs and relief of pruritus.

Results: Fourteen studies with 1137 patients were included. Compared to the control group, PPAR agonists significantly reduced ALP levels by a mean difference of -155.87 U/L (95% confidence interval (CI): -208.30 to -103.44; random-effects). Patients who received PPAR agonists showed a significantly higher biochemical response rate (risk ratio (RR), 4.42; 95% CI: 2.37-8.26; random-effects). Furthermore, there was no significant difference in the rate of severe (RR, 1.05; 95% CI, 0.49-2.28) or serious AEs (RR, 1.02; 95% CI, 0.65-1.60) between the PPAR agonists and placebo groups.

Conclusion: PPAR agonists are effective and safe to treat patients with PBC.

Prospero trial registration: CRD42024545743.