Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival

C. Fiorella Murillo Perez, Stephanie Ioannou, the Global PBC Study Group, Iman Hassanally, Palak J. Trivedi, Christophe Corpechot, Adriaan J. van der Meer, Willem J. Lammers, Pier Maria Battezzati, Keith D. Lindor, Frederik Nevens, Kris V. Kowdley, Tony Bruns, Nora Cazzagon, Annarosa Floreani, Andrew L. Mason, Aliya Gulamhusein, Cyriel Y. Ponsioen, Marco Carbone, Ana LleoMarlyn J. Mayo, George N. Dalekos, Nikolaos K. Gatselis, Douglas Thorburn, Xavier Verhelst, Albert Parés, Maria Carlota Londoño, Harry L.A. Janssen, Pietro Invernizzi, Raj Vuppalanchi, Gideon M. Hirschfield, Bettina E. Hansen, Cynthia Levy*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Background and Aims: Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response. Methods: UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected. Results: For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82–1.33) vs. 2.37 × ULN (1.72–3.69) at six months (p <.001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early. Conclusions: We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.

Original languageEnglish
Pages (from-to)1497-1506
Number of pages10
JournalLiver International
Volume43
Issue number7
DOIs
Publication statusPublished - Jul 2023

Bibliographical note

Funding Information:
This investigator‐initiated study was supported by unrestricted grants from Cymabay Therapeutics Inc., Intercept Pharmaceuticals and previously from Zambon Nederland BV, and was funded by the Toronto General & Western Hospital Foundation (a not‐for‐profit foundation) in Toronto, Canada and the Foundation for Liver and Gastrointestinal Research (a not‐for‐profit foundation) in Rotterdam, the Netherlands. The supporting parties had no influence on the study design, data collection and analyses, writing of the manuscript, or on the decision to submit the manuscript for publication.

Publisher Copyright:
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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