The Efficacy and Safety of Seladelpar for Primary Biliary Cholangitis: A Systematic Review and Meta-Analysis

Seladelpar is an oral, once-daily medication that improves cholestasis through its selective peroxisome proliferator-activated receptor (PPAR-δ) agonism. It shows promising efficacy in treating primary biliary cholangitis (PBC) patients.

A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Cochrane, Scopus, and WOS until July 19th, 2025. Dichotomous outcomes were reported using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI).

Three RCTs with 499 patients were included. Seladelpar was significantly associated with an increased ALP normalization (RR: 21.12 with 95% CI [4.14, 107.58], p < 0.01), biochemical response (RR: 3.06 with 95% CI [2.00, 4.70], p < 0.01), and decreased pruritus NRS score change (MD: -1.47 with 95% CI [-2.73, -0.21], p = 0.02). Seladelpar was also significantly associated with a decreased incidence of pruritus (RR: 0.54 with 95% CI [0.31, 0.94], p = 0.03) but with an increased incidence of headache (RR: 3.37 with 95% CI [1.11, 10.23], p = 0.03). However, there was no significant difference between seladelpar and placebo regarding the incidence of any adverse events (RR: 0.96 with 95% CI [0.87, 1.06], p = 0.43).

Seladelpar improved liver biomarkers of cholestasis and reduced pruritus in patients with PBC without significantly increasing the adverse effects. This makes seladelpar a promising addition to the treatments available for PBC. Trial Registration: PROSPERO: CRD42024521208.