Linerixibat for refractory pruritus in primary biliary cholangitis: a systematic review and meta-analysis

Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease in which pruritus is common, often refractory, and poorly served by current therapies. Linerixibat, an ileal bile acid transporter (IBAT) inhibitor, has been evaluated in randomized controlled trials (RCTs). We conducted a systematic review and meta-analysis of RCTs to assess the efficacy and safety of linerixibat for cholestatic pruritus in PBC. Following PRISMA 2020 and a prospectively registered PROSPERO protocol, five databases were searched to April 2026 for RCTs comparing linerixibat with placebo in adults with PBC and cholestatic pruritus. The primary outcome was change from baseline in the Worst Itch Numerical Rating Scale (WI-NRS). Random-effects meta-analyses used the generic inverse-variance method; the multi-arm trial contributed a single comparison and the crossover trial was entered with within-participant estimates. Certainty of evidence was rated with GRADE. Three RCTs (407 randomized participants; a phase 2a crossover, a phase 2b dose-ranging, and a phase 3 trial) were included. Linerixibat reduced the WI-NRS score compared with placebo (mean difference − 0.95; 95% CI − 1.48 to − 0.42; I² = 47%; moderate certainty) and pruritus-related sleep interference (− 0.68; 95% CI − 1.23 to − 0.13). The proportion of patients achieving a ≥ 2-point WI-NRS reduction did not differ (risk ratio [RR] 1.08; 95% CI 0.91 to 1.28). Serum C4 increased and FGF-19 decreased, consistent with IBAT inhibition; pooled differences in total bile acids and auto-taxin were not statistically significant. Any adverse event (RR 1.22; 95% CI 1.10 to 1.35), diarrhea (RR 3.74; 95% CI 2.58 to 5.43), abdominal pain (RR 3.84; 95% CI 1.83 to 8.08), and discontinuation due to adverse events (RR 3.19; 95% CI 1.36 to 7.48) were more frequent with linerixibat. In adults with PBC, linerixibat produces a modest reduction in pruritus severity and sleep interference, accompanied by more frequent gastrointestinal adverse events and treatment discontinuation. The evidence comprises three trials of differing design with treatment durations of up to 24 weeks; long-term efficacy and safety remain to be established. Not applicable.