Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis.

Barcelona GLOBE Score Meta-analysis Paris-1 Paris-2 Primary biliary cholangitis Rotterdam Systematic review Toronto UDCA response UK-PBC Risk score Ursodeoxycholic acid

Journal

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
ISSN: 1878-3562
Titre abrégé: Dig Liver Dis
Pays: Netherlands
ID NLM: 100958385

Informations de publication

Date de publication:
10 2023
Historique:
received: 26 08 2022
revised: 09 11 2022
accepted: 19 12 2022
medline: 23 10 2023
pubmed: 3 1 2023
entrez: 2 1 2023
Statut: ppublish

Résumé

Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice. This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome. A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed. Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target. The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.

Sections du résumé

BACKGROUND
Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice.
AIMS
This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome.
METHODS
A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed.
RESULTS
Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target.
CONCLUSIONS
The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.

Identifiants

pubmed: 36593158
pii: S1590-8658(22)00834-9
doi: 10.1016/j.dld.2022.12.010
pii:
doi:

Substances chimiques

Ursodeoxycholic Acid 724L30Y2QR
Cholagogues and Choleretics 0
Alkaline Phosphatase EC 3.1.3.1
Bilirubin RFM9X3LJ49

Types de publication

Meta-Analysis Systematic Review Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1318-1327

Informations de copyright

Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest Jakub Gazda, Matej Gazda, Tomas Koky, and Marian Macej declare that they have no conflicts of interest. Sylvia Drazilova, Martin Janicko, and Peter Jarcuska received lecture fees from PRO.MED.CS Praha a. s. Marco Carbone is on the advisory board for Intercept, Perspectum, Mayoly, Calliditas and received lecture fees from Intercept and Mayoly.

Auteurs

Jakub Gazda (J)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.

Sylvia Drazilova (S)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia. Electronic address: sylvia.drazilova@upjs.sk.

Matej Gazda (M)

Intelligent Information Systems Laboratory, Technical University of Kosice, Bozeny Nemcovej 32, 04201 Kosice, Slovakia.

Martin Janicko (M)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.

Tomas Koky (T)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.

Marian Macej (M)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.

Marco Carbone (M)

Division of Gastroenterology and Centre for Autoimmune Liver Disease, University of Milano-Bicocca, Piazza dell'Ateneo Nuovo, 1, 20126 Milano, Italy.

Peter Jarcuska (P)

2nd Department of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Trieda SNP 1, 040 12, Kosice, Slovakia.

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