{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:00:21Z","timestamp":1792839621587,"version":"4.5.0"},"reference-count":74,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100018262","name":"Intercept Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018262","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020406","name":"Dr. Falk Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020406","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Biochemical non\u2010response to ursodeoxycholic acid, as a first\u2010line therapy, is associated with a heightened risk of clinical events in primary biliary cholangitis (PBC). Herein, we determine whether biochemical non\u2010response to second\u2010line therapy in obeticholic acid (OCA) is also predictive of long\u2010term event\u2010free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Data were collected from patients who initiated OCA at large, high\u2010volume centres in the UK, Italy, and Canada between August 2017 and 2019, with follow\u2010up continuing until June 2024. Biochemical non\u2010response was defined by POISE criteria. Clinical events were defined as hepatic decompensation, referral for transplantation, hepatocellular carcinoma, or death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our cohort consisted of 336 patients (29% with cirrhosis), of whom\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009150 (45%) discontinued OCA over 48\u2009months. Over 851 patient\u2010years of OCA use, without the addition of another PBC therapy,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009230,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009192,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009158 and\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009150 patients completed 12, 24, 36 and 48\u2009months follow\u2010up, respectively. Of this cohort, 37%, 48%, 63% and 55% attained biochemical response, with 7%, 14%, 25% and 19% normalising ALP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01; all comparisons vs. baseline). Over 4\u2009years, 64 patients experienced a clinical event. Twelve\u2010month biochemical non\u2010response associated with a heightened risk of clinical events (hazard ratio [HR]: 4.50; 95% CI: 1.74\u201320.23), as did cirrhosis (HR: 20.24, 10.15\u201340.32), hyperbilirubinaemia (HR: 2.55, 1.71\u20133.76), hypoalbuminaemia (HR: 0.92, 0.90\u20130.96) and thrombocytopenia (HR: 0.99, 0.98\u20130.99). The prognostic utility of biochemical non\u2010response (HR: 3.29, 1.72\u201314.96) and cirrhosis (HR: 19.67, 5.09\u201376.08) persisted on multivariable analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Biochemical response stratifies risk of clinical events in PBC patients under OCA treatment. Whilst response rates increase over time, discontinuation rates underscore the need for newer treatment paradigms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70378","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T07:49:41Z","timestamp":1758527381000},"page":"494-506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Non\u2010Response to Obeticholic Acid Is Associated With Heightened Risks of Developing Clinical Events in Primary Biliary Cholangitis"],"prefix":"10.1111","volume":"63","author":[{"given":"Nadir","family":"Abbas","sequence":"first","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre Centre for Liver and Gastrointestinal Research, University of Birmingham  UK"},{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"},{"name":"Institute of Immunology, Immunity and Immunotherapy University of Birmingham  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Smith","sequence":"additional","affiliation":[{"name":"Academic Department of Medical Genetics University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellina","family":"Lytvyak","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Liver Unit University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Scaravaglio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Halliday","sequence":"additional","affiliation":[{"name":"Institute of Liver and Digestive Health, University College London  London UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Almahroos","sequence":"additional","affiliation":[{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Eden","sequence":"additional","affiliation":[{"name":"Institute of Liver and Digestive Health, University College London  London UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Lloyd\u2010Madden","sequence":"additional","affiliation":[{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanchit","family":"Sharma","sequence":"additional","affiliation":[{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2529-0409","authenticated-orcid":false,"given":"James","family":"Ferguson","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre Centre for Liver and Gastrointestinal Research, University of Birmingham  UK"},{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"},{"name":"Institute of Immunology, Immunity and Immunotherapy University of Birmingham  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6733-5225","authenticated-orcid":false,"given":"Jessica K.","family":"Dyson","sequence":"additional","affiliation":[{"name":"Department of Hepatology Newcastle Upon Tyne Hospital NHS Foundation Trust  Newcastle UK"},{"name":"NIHR Newcastle Biomedical Research Centre Newcastle University  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Thorburn","sequence":"additional","affiliation":[{"name":"Institute of Liver and Digestive Health, University College London  London UK"},{"name":"Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Hepatology Newcastle Upon Tyne Hospital NHS Foundation Trust  Newcastle UK"},{"name":"NIHR Newcastle Biomedical Research Centre Newcastle University  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2511-7980","authenticated-orcid":false,"given":"Aldo J.","family":"Montano\u2010Loza","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Liver Unit University of Alberta  Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1445-0443","authenticated-orcid":false,"given":"Marco","family":"Carbone","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3262-1998","authenticated-orcid":false,"given":"Pietro","family":"Invernizzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2010Bicocca  Milan Italy"},{"name":"Division of Gastroenterology Center for Autoimmune Liver Diseases, European Reference Network on Hepatological Diseases (ERN RARE\u2010LIVER), IRCCS Fondazione San Gerardo Dei Tintori  Monza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Mells","sequence":"additional","affiliation":[{"name":"Academic Department of Medical Genetics University of Cambridge  Cambridge UK"},{"name":"Department of Hepatology Newcastle Upon Tyne Hospital NHS Foundation Trust  Newcastle UK"},{"name":"NIHR Newcastle Biomedical Research Centre Newcastle University  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Culver","sequence":"additional","affiliation":[{"name":"Translational Gastroenterology and Liver Unit, John Radcliffe Hospital, Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4009-8087","authenticated-orcid":false,"given":"Palak J.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre Centre for Liver and Gastrointestinal Research, University of Birmingham  UK"},{"name":"Liver Unit, University Hospitals Birmingham Queen Elizabeth  Birmingham UK"},{"name":"Institute of Immunology, Immunity and Immunotherapy University of Birmingham  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31607-X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2015.187"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199105303242204"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405123301903"},{"issue":"6","key":"e_1_2_9_6_1","first-page":"1668","article-title":"Ten\u2010Year Survival in Ursodeoxycholic Acid\u2010Treated Patients With Primary Biliary Cirrhosis","volume":"29","author":"Poupon R. E.","year":"1999","journal-title":"UDCA\u2010PBC Study Group. Hepatology"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(94)90021-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190512"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840220311"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(00)80216-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290301"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2000.20240"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)11293-X"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.04.001"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28017"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.029"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.12.029"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.02.031"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22428"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.01.003"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.216"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.06.062"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001166"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.02.005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.112"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32117"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102017\u2010315259"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(11)60030-5"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.12.005"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30094-9"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.08.054"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-322362"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003029"},{"key":"e_1_2_9_36_1","unstructured":"European Medicines Agency (EMA) \u201cOcaliva\u2014Referral 2024\u201d https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/ocaliva."},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001174"},{"key":"e_1_2_9_38_1","unstructured":"NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE (NICE) \u201cObeticholic Acid for Treating Primary Biliary Cholangitis. Final Apprais Determ 2017\u201d."},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.07.038"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2021.100248"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.06.017"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2024.0987"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000557"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.01.029"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306185"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312100"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16336"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18004"},{"key":"e_1_2_9_49_1","unstructured":"Intercept Pharmaceuticals \u201cA Phase 3 Open\u2010Label Long\u2010Term Safety Extension Study Evaluating the Safety and Tolerability of the Fixed\u2010Dose Combination of Obeticholic Acid and Bezafibrate in Subjects With Primary Biliary Cholangitis\u201d https:\/\/clinicaltrials.gov\/study\/NCT06488911."},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1518"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16181"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.05.008"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001343"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15386"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000826"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(24)01085-7"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31017"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0000000000000841"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1407963"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa012"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2023.04.010"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007995.2015.1053048"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.5879"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000529"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17755"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(24)00607-X"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000395"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003174"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000612"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15982"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.10.032"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30319-7"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100931"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000002464"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15554"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70378","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apt.70378","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.70378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T19:28:53Z","timestamp":1771010933000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.70378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":74,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/apt.70378"],"URL":"https:\/\/doi.org\/10.1111\/apt.70378","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]},"assertion":[{"value":"2025-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}