Meta‐Analysis: PPAR Agonists for Pruritus and Quality of Life in Primary Biliary Cholangitis

BACKGROUND AND AIMS: Pruritus is a frequent and debilitating symptom in primary biliary cholangitis (PBC), substantially impairing sleep, mood and quality of life. Peroxisome proliferator-activated receptor (PPAR) agonists are promising second-line therapies for patients with an inadequate response to ursodeoxycholic acid (UDCA). We conducted a systematic review and meta-analysis to evaluate the efficacy of PPAR agonists on pruritus and health-related quality of life (HRQoL) in PBC. METHODS: We systematically searched for randomised placebo-controlled trials (RCTs) of PPAR agonists in PBC through December 2025. Eligible studies reported validated pruritus or HRQoL outcomes. Main outcomes were NRS and PBC-40 total score. Pooled estimates were calculated using random-effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). RESULTS: Five RCTs evaluating bezafibrate, elafibranor and seladelpar (n = 660; 390 PPAR agonist; 270 placebo) met the inclusion criteria. For pruritus intensity analyses, data were restricted to participants with moderate-to-severe baseline symptoms (NRS ≥ 4) when available. PPAR agonists significantly reduced NRS scores at 3 months (MD, -1.39; 95% CI: -2.49 to -0.29), 6 months (MD, -1.17; 95% CI: -1.96 to -0.38) and 12 months (MD, -1.73; 95% CI, -3.00 to -0.46); in individual agent analyses, bezafibrate and seladelpar reached statistical significance at two or more time points. While improvements were also noted in PBC-40 itch-domain and 5D-itch score, an impact on overall HRQoL as reflected by PBC-40 total score could not be demonstrated, with a lower level of certainty. CONCLUSIONS: PPAR agonists, notably bezafibrate and seladelpar, reduce pruritus severity in PBC patients with moderate-to-severe symptoms and consistently improve itch-specific outcomes. However, effects on global HRQoL remain uncertain. These findings underscore the incorporation of validated, symptom-focused endpoints in future PBC trials.