{ "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.\n\nMethods:: 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).\n\nResults:: 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).\n\nConclusion:: 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.", "abstract_shown": true, "affiliations": [ "Department of Medicine, Shaheed Mohtarma Benazir Bhutto Medical College Lyari, Karachi, Pakistan", "Department of Medicine, Ziauddin Medical College, Karachi, Pakistan", "Department of Medicine, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan", "Department of Pharmacy, Shaheed Mohtarma Benazir Bhutto Medical University Institute of Pharmacy, Larkana, Pakistan", "Department of Medicine, Patan Academy of Health Sciences, Lalitpur, Nepal." ], "article_type": "research article", "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0 ], "name": "Mukesh Kumar", "orcid": "0009-0000-7527-109X" }, { "affs": [ 1 ], "name": "Vivek Kumar" }, { "affs": [ 2 ], "name": "Syeda Warisha" }, { "affs": [ 0 ], "name": "Sumet Kumar", "orcid": "0009-0004-2215-311X" }, { "affs": [ 0 ], "name": "Munazzah Khan" }, { "affs": [ 0 ], "name": "Mahwish Gulbahar" }, { "affs": [ 0 ], "name": "Savera Shabbir" }, { "affs": [ 0 ], "name": "Laksh Kumar" }, { "affs": [ 0 ], "name": "Rehma Binte Nasir" }, { "affs": [ 2 ], "name": "Usba Rafique" }, { "affs": [ 3 ], "name": "Murk Kumari Pamnani" }, { "affs": [ 2 ], "name": "Um E Farwa" }, { "affs": [ 2 ], "name": "Surhan Indra" }, { "affs": [ 0 ], "name": "FNU Poonam" }, { "affs": [ 0 ], "name": "FNU Bakhtawar" }, { "affs": [ 4 ], "name": "Aayush Chaulagain", "orcid": "0009-0001-9259-0612" } ], "bibtex": "https://research.draconitic.com/paper/716ev8m7qxdxd.bib", "cited_by": 0, "doi": "10.1097/md.0000000000051203", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727225/?tool=EBI", "id": "716ev8m7qxdxd", "issns": [ "0304-5412", "1536-5964", "0025-7974" ], "landing_url": "https://europepmc.org/article/PMC/PMC13727225", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "4000" ], [ "heading", "Research Article" ], [ "heading", "Systematic Review and Meta-Analysis" ] ], "openalex": null, "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13727225/pdf/?tool=EBI", "pmcid": "PMC13727225", "pmid": null, "published": "2026-10-30", "publisher": "Wolters Kluwer Health", "ris": "https://research.draconitic.com/paper/716ev8m7qxdxd.ris", "sources": [ { "first_seen": "2026-11-03T15:20:51Z", "native_id": "PMC:PMC13727225", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13727225" }, { "first_seen": "2026-11-05T12:23:21Z", "native_id": "PMC13727225", "source": "pmc", "url": "https://doi.org/10.1097/md.0000000000051203" } ], "subjects": [ { "field": "medicine", "origin": "journal-openalex:F27", "subfield": "general" } ], "title": "The role of linerixibat in treating pruritus in primary biliary cholangitis : A systematic review and meta-analysis of randomised controlled trials", "title_text": "The role of linerixibat in treating pruritus in primary biliary cholangitis : A systematic review and meta-analysis of randomised controlled trials", "type": "peer-reviewed", "updated_at": "2026-11-06T12:22:57Z", "url": "https://research.draconitic.com/paper/716ev8m7qxdxd", "venue": "Medicine", "versions": [] }