@article{19a5f7dadd55452c865d5e9d59648177,
title = "Liver transplant-free survival according to alkaline phosphatase and GLOBE score in patients with primary biliary cholangitis treated with ursodeoxycholic acid",
abstract = "Background: After 1 year of ursodeoxycholic acid (UDCA), patients with primary biliary cholangitis (PBC) may have a normal GLOBE score despite high alkaline phosphatase (ALP) levels. Aim: To assess the association between ALP and liver transplantation (LT)-free survival according to the GLOBE score. Methods: Among patients with a normal or elevated GLOBE score in the Global PBC cohort, the association between ALP after 1 year of UDCA and the risk of LT/death was assessed. The LT-free survival was compared with that of a matched general population. Results: After 1 year of UDCA, ALP was associated with the risk of LT/death (aHR 1.31, 95% CI 1.003–1.72, p = 0.048) among 2729 patients with a normal GLOBE score. The 10-year LT-free survival among these patients with an ALP >2.0 × ULN was 94.0% (95% CI 90.1–97.9) for those <50 years, and 82.6% (95% CI 76.5–88.7) for those ≥50 years, which was significantly lower (p = 0.040) and similar (p = 0.736) to that of the matched population, respectively. The 10-year LT-free survival in patients ≥50 years with normal GLOBE score and normal ALP (90.8%, 95% CI 87.7–93.9) was significantly higher (p = 0.022) than the matched population. Among 1045 patients with an elevated GLOBE score, ALP was associated with LT/death only in those <50 years (aHR 1.38, 95% CI 1.06–1.81, p = 0.016). Conclusion: The LT-free survival of patients with PBC with a normal GLOBE score is optimal in case of normal ALP levels, also in relation to the general population. Despite their generally favourable prognosis, an elevated ALP level may still indicate a need for add-on therapy.",
keywords = "GLOBE score, primary biliary cholangitis, second-line treatment, treatment response",
author = "{the GLOBAL PBC Study Group} and {de Veer}, {Rozanne C.} and Harms, {Maren H.} and Christophe Corpechot and Douglas Thorburn and Pietro Invernizzi and Janssen, {Harry L.A.} and Battezzati, {Pier M.} and Frederik Nevens and Lindor, {Keith D.} and Annarosa Floreani and Ponsioen, {Cyriel Y.} and Mayo, {Marlyn J.} and Albert Par{\'e}s and Mason, {Andrew L.} and Kowdley, {Kris V.} and Trivedi, {Palak J.} and Hirschfield, {Gideon M.} and Tony Bruns and Dalekos, {George N.} and Gatselis, {Nikolaos K.} and Xavier Verhelst and Lammers, {Willem J.} and Hansen, {Bettina E.} and {van Buuren}, {Henk R.} and {van der Meer}, {Adriaan J.}",
note = "Funding Information: The following authors declared that they have no conflicts of interest: Rozanne C. de Veer and Pier M. Battezzati. Maren H. Harms received a speakers fee from Zambon Nederland B.V. and thesis printing reimbursements from Intercept Pharmaceuticals, Pentax, Norgine, Tramedico, Dr. Falk, Sysmex, Astellas and Zambon Nederland B.V. Christophe Corpechot reports receiving consulting fees from Intercept Pharmaceuticals, Cymabay, Genkyotex and Inventiva, grant support from Arrow and Intercept Pharmaceuticals, and fees for teaching from GlaxoSmithKline. Douglas Thorburn reports consulting activities for Intercept Pharmaceuticals. Pietro Invernizzi reports personal fees from Intercept and non‐financial support from Bruschettini and Menarini Diagnostics. Harry L.A. Janssen reports grants from and consulting work for AbbVie Pharmaceuticals, Bristol‐Myers Squibb, Gilead Sciences, Innogenetics, Merck, Novartis, Roche, Intercept Pharmaceuticals and Janssen. Frederik Nevens reports Advisory boards for Astellas, Janssen‐Cilag, AbbVie, Gilead, CAF, Intercept, Gore, BMS, Novartis, MSD, Janssen‐Cilag, Promethera Biosciences, Ono Pharma, Durect, Roche, Ferring. Research grants from Roche, Ferring and Novartis. Keith D. Lindor reports that he is an unpaid advisor for Intercept Pharmaceuticals and Shire. Annerosa Floreani reports consulting activities for Intercept Pharmaceuticals. Cyriel Y. Ponsioen has received grant support from Takeda, speaker's fees from Tillotts and Takeda, consultancy fee from Pliant and served as consultant for Takeda. Marlyn J. Mayo reports being on advisory committees or review panels for GSK, Target, Regeneron; grant/research support from Cymabay, Intercept, Mallinckrodt, Target, GSK and Salix. Albert Par{\'e}s reports consulting services for Intercept Pharmaceuticals and Novartis Pharma. Andrew L. Mason reports advisory services for Intercept Pharmaceuticals, AbbVie and Novartis; and research funding resources from the Canadian Institutes of Health Research, Canadian Liver Foundation, American Kennel Club, Intercept Pharmaceuticals Inc., AbbVie and Gilead Sciences. Kris V. Kowdley reports personal fees from Gilead Sciences, Intercept Pharmaceuticals and Novartis; and grants from Gilead Sciences and Intercept Pharmaceuticals. Palak J. Trivedi receives institutional salary support from the NIHR Birmingham Liver Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. PJT has received research grant funding from the Wellcome trust, the Core Digestive Diseases Charity, Intercept Pharmaceuticals, Bristol Myers' Squibb, Innovate UK, the Medical Research Foundation, EASL and PSC Support. He has also received speaker fees from Dr. Falk Pharma, Intercept Pharmaceuticals and Perspectum Diagnostics. He has received consulting and advisory board fees from Dr. Falk Pharma, Intercept Pharmaceuticals and GSK. Gideon M. Hirschfield reports advisory services for Intercept Pharmaceuticals, Novartis and GlaxoSmithKline Pharmaceuticals. Tony Bruns has received honoraria from Intercept Pharmaceuticals, Falk Foundation, Abbvie and Norgine, and travel expenses from Gilead. George N Dalekos is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, Sobi, received research grants from Abbvie, Gilead and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc. and Intercept Pharmaceuticals. Nikolaos K. Gatselis is an advisor or lecturer for Gilead and has acted as co‐investigator in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc. and Intercept Pharmaceuticals. Xavier Verhelst received grants from Gilead, Abbvie, Dr Phalk Pharma and MSD and acted as a consultant for Gilead, Abbvie and MSD. Willem J. Lammers reports consulting services for Intercept Pharmaceuticals. Bettina E. Hansen reports grants from Intercept Pharmaceuticals, Cymabay Therapeutics and Zambon Nederland B.V. and consulting work for Intercept Pharmaceuticals, Cymabay Therapeutics, Albireo AB and Novartis. Henk R. van Buuren is a consultant for Intercept Pharma Benelux and received unrestricted research grants from Intercept Pharmaceuticals and from Zambon Nederland B.V. A.J. van der Meer reports speakers fees from Zambon Nederland B.V., received an unrestricted grant from Gilead Sciences, AbbVie, MSD and Zambon Nederland B.V. and consulting work for AOP Pharma. Funding Information: This investigator‐initiated study was supported by an unrestricted grant from Intercept Pharmaceuticals and was funded by 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: {\textcopyright} 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.",
year = "2022",
month = nov,
doi = "10.1111/apt.17226",
language = "English (US)",
volume = "56",
pages = "1408--1418",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",
number = "9",
}