PPAR agonists in Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Introduction Agonists of the peroxisome proliferator-activated receptor (PPAR) have attracted attention for their potential to treat primary biliary cholangitis (PBC). However, individual trials lack sufficient power to detect significant differences in clinical and laboratory outcomes. Objectives This meta-analysis aims to compare PPAR agonists versus placebo or standard treatment in patients with PBC. Methods We systematically searched PubMed, Embase and Cochrane for studies comparing PPAR agonists with placebo or standard-of-care treatment in PBC. The primary outcomes were pruritus, alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total and direct bilirubin levels. We performed statistical analyses using R 4.1.1. Heterogeneity was examined with the Cochran Q test and I² statistics. We computed risk ratios (RR), mean differences (MD), and Standardized Mean Differences (SMD), with 95% confidence intervals (CI), using a random-effects model. Results Thirteen randomized controlled trials were included in this meta-analysis, comprising 1,124 patients, of whom 687 (57%) received PPAR agonists plus UDCA. When compared with control, PPAR analogs were significantly associated with a reduction in pruritus (RR 0.63; 95% CI 0.41 to 0.96; p = 0.031; I²=9%), ALP (MD -130.93; 95% CI -156.44 to -105.42; p < 0.01; I²=84%), GGT (MD -39.83; 95% CI -78.44 to -1.22; p = 0.04; I²=94%) and total bilirubin levels (SMD − 0.03; 95% CI -0.06 to -0.01; p < 0.01; I²=69%). Conclusion The use of PPAR agonists reduced the incidence of pruritus and the levels of ALP, GGT, and total bilirubin in patients with PBC.