Clinical, safety, and patient-reported outcomes associated with second-line and later therapies in primary biliary cholangitis: A systematic review
5 affiliations
- 1Division of Gastroenterology and Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
- 2Institute of Cellular Medicine and NIHR Newcastle Biomedical Research Centre, Newcastle University, Newcastle Upon Tyne, UK
- 3Ipsen, London, UK
- 4Costello Medical, Cambridge, UK
- 5Department of Internal Medicine II, Saarland University Medical Center, Homburg, Germany
Abstract
Background
Primary biliary cholangitis (PBC) is a rare, chronic, cholestatic disease that can result in cirrhosis, liver failure, and death. While biochemical markers such as alkaline phosphatase (ALP) and total bilirubin (TB) measure disease activity and progression, definitions of biochemical response vary. This systematic literature review (SLR) identified clinical studies for investigational and approved treatments in patients with PBC with inadequate response or intolerance to ursodeoxycholic acid requiring second-line (2L) or later (2L+) therapies.Methods
Electronic databases were searched on August 7, 2025 (MEDLINE; Embase) or September 30, 2025 (Cochrane Database of Systematic Reviews; CENTRAL), and conference proceedings (2021-2025), bibliographies, and ClinicalTrials.gov were searched on August 15, 2025, following a pre-specified protocol (PROSPERO ID: CRD42023382262). Interventional and observational studies in the 2L/2L+ setting were prioritized for inclusion, and randomized controlled trials for extraction.Results
A total of 149 publications on 44 unique studies were included. Phase III trials evaluated elafibranor, seladelpar, budenoside, bezafibrate, and obeticholic acid. Various composite biochemical response endpoints were reported across 34% of studies, most frequently the POISE criteria (18%). Biochemical markers were assessed frequently (ALP: 89%; TB: 71%); however, upper limits of normal and response thresholds varied substantially. Response rates in placebo-controlled trials favored active treatment, although placebo responses were highly variable. Non-invasive fibrosis measures were reported in 16% of studies and showed small short-term changes. Patient-reported outcomes assessed pruritus (52%) and fatigue (32%) using a variety of scales.Conclusion
The evidence base for 2L/2L+ PBC therapies is extensive but heterogeneous in study designs, patient populations, and treatment assessment scales and outcome definitions, limiting cross-trial comparisons. This SLR provides a robust foundation for contextualizing study outcomes within the broader landscape and supporting clinical decision-making.
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BibTeX
@article{carbone2026clinical,
title = {{Clinical, safety, and patient-reported outcomes associated with second-line and later therapies in primary biliary cholangitis: A systematic review}},
author = {Marco Carbone and David Jones and Oyinkan Solanke and Rikke Brandt and Taryn Krause and Darren Asquith and Alex Pashley and Sonia Shaw and Emma Worthington and Jörn M. Schattenberg},
journal = {Hepatology communications},
year = {2026},
month = oct,
doi = {10.1097/hc9.0000000000001048},
url = {https://europepmc.org/article/PMC/PMC13668302},
note = {CC BY},
}
RIS
TY - JOUR
TI - Clinical, safety, and patient-reported outcomes associated with second-line and later therapies in primary biliary cholangitis: A systematic review
AU - Marco Carbone
AU - David Jones
AU - Oyinkan Solanke
AU - Rikke Brandt
AU - Taryn Krause
AU - Darren Asquith
AU - Alex Pashley
AU - Sonia Shaw
AU - Emma Worthington
AU - Jörn M. Schattenberg
PY - 2026
DA - 2026/10/14
JO - Hepatology communications
DO - 10.1097/hc9.0000000000001048
UR - https://europepmc.org/article/PMC/PMC13668302
AB - Background Primary biliary cholangitis (PBC) is a rare, chronic, cholestatic disease that can result in cirrhosis, liver failure, and death. While biochemical markers such as alkaline phosphatase (ALP) and total bilirubin (TB) measure disease activity and progression, definitions of biochemical response vary. This systematic literature review (SLR) identified clinical studies for investigational and approved treatments in patients with PBC with inadequate response or intolerance to ursodeoxycholic acid requiring second-line (2L) or later (2L+) therapies.Methods Electronic databases were searched on August 7, 2025 (MEDLINE; Embase) or September 30, 2025 (Cochrane Database of Systematic Reviews; CENTRAL), and conference proceedings (2021-2025), bibliographies, and ClinicalTrials.gov were searched on August 15, 2025, following a pre-specified protocol (PROSPERO ID: CRD42023382262). Interventional and observational studies in the 2L/2L+ setting were prioritized for inclusion, and randomized controlled trials for extraction.Results A total of 149 publications on 44 unique studies were included. Phase III trials evaluated elafibranor, seladelpar, budenoside, bezafibrate, and obeticholic acid. Various composite biochemical response endpoints were reported across 34% of studies, most frequently the POISE criteria (18%). Biochemical markers were assessed frequently (ALP: 89%; TB: 71%); however, upper limits of normal and response thresholds varied substantially. Response rates in placebo-controlled trials favored active treatment, although placebo responses were highly variable. Non-invasive fibrosis measures were reported in 16% of studies and showed small short-term changes. Patient-reported outcomes assessed pruritus (52%) and fatigue (32%) using a variety of scales.Conclusion The evidence base for 2L/2L+ PBC therapies is extensive but heterogeneous in study designs, patient populations, and treatment assessment scales and outcome definitions, limiting cross-trial comparisons. This SLR provides a robust foundation for contextualizing study outcomes within the broader landscape and supporting clinical decision-making.
SN - 2471-254X
ER -