The role of linerixibat in treating pruritus in primary biliary cholangitis : A systematic review and meta-analysis of randomised controlled trials
5 affiliations
- 1Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan
- 2Department of Medicine, Ziauddin Medical College, Karachi, Pakistan
- 3Department of Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan
- 4Department of Pharmacy, Shaheed Mohtarma Benazir Bhutto Medical University Institute of Pharmacy, Larkana, Pakistan
- 5Department of Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal.
Abstract
Background:: Cholestatic pruritus affects up to 89% of patients with primary biliary cholangitis (PBC) and responds poorly to conventional treatment. Linerixibat, an oral ileal bile acid transporter inhibitor, was approved by the Food and Drug Administration in March 2026 as the first medicine indicated specifically for cholestatic-pruritus in PBC. This meta-analysis evaluated its efficacy, safety and pharmacodynamic effects.
Methods:: PubMed, Google Scholar, ScienceDirect, the Cochrane Library and ClinicalTrials.gov were searched from inception to April 2026 for randomized, placebo-controlled trials of linerixibat in adults with PBC and cholestatic pruritus. To avoid unit-of-analysis error, only period 1 data were used from the phase 2a crossover trial, and the shared placebo group of the multi-arm phase 2b trial was divided proportionally across active arms. Random-effects (DerSimonian–Laird) models generated mean differences (MD), standardized mean differences and risk ratios (RRs) with 95% confidence intervals. Certainty was rated using Grading of Recommendations, Assessment, Development and Evaluations (PROSPERO CRD420261381897).
Results:: Three trials randomizing 407 participants were included. Linerixibat reduced Worst Itch Numerical Rating Scale (WI-NRS) score versus placebo (MD −0.71; 95% confidence interval: −1.12 to −0.30; P = .0007; I2 = 0%), below the 2 to 3 point minimal clinically important difference. Sleep interference improved modestly (MD −0.47; P = .04). Responder rates were not significant at ≥2 points (RR 1.06; P = .49), borderline at ≥3 points (RR 1.25; P = .05), and nonsignificant at ≥4 points (RR 1.23; P = .10). Neither the PBC-40 itch domain (P = .14) nor 5-D Itch Scale (P = .28) differed significantly. Target engagement was confirmed by reduced total serum bile acids (P = .003) and fibroblast growth factor 19 (P = .0005) and increased 7α-hydroxy-4-cholesten-3-one (P < .00001); autotaxin was unchanged (standardized mean difference −0.20; P = .27). Overall adverse events were not significantly increased (RR 1.38; P = .06), but discontinuation (RR 2.75; P = .009), diarrhea (RR 3.69), abdominal pain (RR 2.80) and dyspepsia (RR 7.22) were significantly more frequent with linerixibat. Results at the licensed 40 mg twice-daily dose were concordant (WI-NRS MD −0.75; P = .003).
Conclusion:: Linerixibat produces a statistically significant but modest reduction in itch intensity below the accepted minimal clinically important difference, alongside a substantial gastrointestinal tolerability burden and roughly 3-fold increase in discontinuation. It is a mechanistically validated, licensed option for refractory cholestatic pruritus, but benefit-harm trade-offs should be discussed explicitly with patients. Grading of Recommendations, Assessment, Development and Evaluations certainty was moderate for the primary outcome.
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BibTeX
@article{kumar2026role,
title = {{The role of linerixibat in treating pruritus in primary biliary cholangitis : A systematic review and meta-analysis of randomised controlled trials}},
author = {Mukesh Kumar and Vivek Kumar and Syeda Warisha and Sumet Kumar and Munazzah Khan and Mahwish Gulbahar and Savera Shabbir and Laksh Kumar and Rehma Binte Nasir and Usba Rafique and Murk Kumari Pamnani and Um E Farwa and Surhan Indra and FNU Poonam and FNU Bakhtawar and Aayush Chaulagain},
journal = {Medicine},
year = {2026},
month = oct,
doi = {10.1097/md.0000000000051203},
url = {https://europepmc.org/article/PMC/PMC13727225},
note = {CC BY},
}
RIS
TY - JOUR
TI - The role of linerixibat in treating pruritus in primary biliary cholangitis : A systematic review and meta-analysis of randomised controlled trials
AU - Mukesh Kumar
AU - Vivek Kumar
AU - Syeda Warisha
AU - Sumet Kumar
AU - Munazzah Khan
AU - Mahwish Gulbahar
AU - Savera Shabbir
AU - Laksh Kumar
AU - Rehma Binte Nasir
AU - Usba Rafique
AU - Murk Kumari Pamnani
AU - Um E Farwa
AU - Surhan Indra
AU - FNU Poonam
AU - FNU Bakhtawar
AU - Aayush Chaulagain
PY - 2026
DA - 2026/10/30
JO - Medicine
DO - 10.1097/md.0000000000051203
UR - https://europepmc.org/article/PMC/PMC13727225
AB - Background:: Cholestatic pruritus affects up to 89% of patients with primary biliary cholangitis (PBC) and responds poorly to conventional treatment. Linerixibat, an oral ileal bile acid transporter inhibitor, was approved by the Food and Drug Administration in March 2026 as the first medicine indicated specifically for cholestatic-pruritus in PBC. This meta-analysis evaluated its efficacy, safety and pharmacodynamic effects. Methods:: PubMed, Google Scholar, ScienceDirect, the Cochrane Library and ClinicalTrials.gov were searched from inception to April 2026 for randomized, placebo-controlled trials of linerixibat in adults with PBC and cholestatic pruritus. To avoid unit-of-analysis error, only period 1 data were used from the phase 2a crossover trial, and the shared placebo group of the multi-arm phase 2b trial was divided proportionally across active arms. Random-effects (DerSimonian–Laird) models generated mean differences (MD), standardized mean differences and risk ratios (RRs) with 95% confidence intervals. Certainty was rated using Grading of Recommendations, Assessment, Development and Evaluations (PROSPERO CRD420261381897). Results:: Three trials randomizing 407 participants were included. Linerixibat reduced Worst Itch Numerical Rating Scale (WI-NRS) score versus placebo (MD −0.71; 95% confidence interval: −1.12 to −0.30; P = .0007; I2 = 0%), below the 2 to 3 point minimal clinically important difference. Sleep interference improved modestly (MD −0.47; P = .04). Responder rates were not significant at ≥2 points (RR 1.06; P = .49), borderline at ≥3 points (RR 1.25; P = .05), and nonsignificant at ≥4 points (RR 1.23; P = .10). Neither the PBC-40 itch domain (P = .14) nor 5-D Itch Scale (P = .28) differed significantly. Target engagement was confirmed by reduced total serum bile acids (P = .003) and fibroblast growth factor 19 (P = .0005) and increased 7α-hydroxy-4-cholesten-3-one (P < .00001); autotaxin was unchanged (standardized mean difference −0.20; P = .27). Overall adverse events were not significantly increased (RR 1.38; P = .06), but discontinuation (RR 2.75; P = .009), diarrhea (RR 3.69), abdominal pain (RR 2.80) and dyspepsia (RR 7.22) were significantly more frequent with linerixibat. Results at the licensed 40 mg twice-daily dose were concordant (WI-NRS MD −0.75; P = .003). Conclusion:: Linerixibat produces a statistically significant but modest reduction in itch intensity below the accepted minimal clinically important difference, alongside a substantial gastrointestinal tolerability burden and roughly 3-fold increase in discontinuation. It is a mechanistically validated, licensed option for refractory cholestatic pruritus, but benefit-harm trade-offs should be discussed explicitly with patients. Grading of Recommendations, Assessment, Development and Evaluations certainty was moderate for the primary outcome.
SN - 0304-5412
SN - 1536-5964
SN - 0025-7974
ER -