{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:38:25Z","timestamp":1791005905962,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014382","name":"Ipsen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014382","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background & Aims<\/jats:title>\n Baseline alkaline phosphatase (ALP) levels can influence the likelihood of achieving dichotomous biochemical response criteria in primary biliary cholangitis (PBC). This concept was explored using Week 52 data from the phase III ELATIVE trial (NCT04526665), which assessed elafibranor, a peroxisome proliferator\u2010activated receptor \u03b1\/\u03b4 agonist approved as a second\u2010line treatment for PBC.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Patients were grouped by baseline ALP. Outcomes assessed: biochemical response, ALP normalization, ALP change from baseline (CfB), transplant\u2010free survival (using GLOBE score).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n At Week 52, biochemical response was achieved across all subgroups receiving elafibranor (\u2264\u20092\u00d7 upper limit of normal [ULN]: 86.7%,\u2009>\u20092\u2013\u2264\u20092.5\u00d7 ULN: 80.0%, >\u20092.5\u2013\u2264\u20093\u00d7 ULN: 52.0%, >\u20093\u2013\u2264\u20094\u00d7 ULN: 22.2%, >\u20094\u00d7 ULN: 18.8%), and one subgroup receiving placebo (\u2264\u20092\u00d7 ULN: 13.3%). ALP normalization occurred only with elafibranor (\u2264\u20092\u00d7 ULN: 53.3%,\u2009>\u20092\u2013\u2264\u20092.5\u00d7 ULN: 12.0%, >\u20092.5\u2013\u2264\u20093\u00d7 ULN: 12.0%, >\u20094\u00d7 ULN: 12.5%). Mean ALP reductions were consistent across subgroups receiving elafibranor (overall CfB: \u221238.9%). Patients receiving elafibranor, regardless of biochemical response, had similar reductions in risk of liver transplant and\/or liver\u2010related mortality within 15\u2009years (\u22124.0% to \u22124.5%); among patients receiving placebo, reduced risk was only predicted in responders (\u22121.5%).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In ELATIVE, lower baseline ALP correlated with higher biochemical response and ALP normalization rates with elafibranor. However, among patients receiving elafibranor, relative reductions in risk scores and ALP were consistent regardless of biochemical response and pre\u2010treatment ALP, indicating treatment benefit. Similar biochemical benefits were not observed among patients receiving placebo. These results support evaluating continuous measures and prognostic scores alongside dichotomous criteria to comprehensively assess efficacy.<\/jats:p>\n \n Trial Registration<\/jats:bold>\n : NCT04526665\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70630","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:15:26Z","timestamp":1775459726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Baseline Alkaline Phosphatase Impacts Response Rates in Primary Biliary Cholangitis: Exploring Response to Elafibranor in\n ELATIVE<\/scp>"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-6037","authenticated-orcid":false,"given":"Cynthia","family":"Levy","sequence":"first","affiliation":[{"name":"Schiff Center for Liver Diseases University of Miami Miami Florida USA"},{"name":"Division of Digestive Health and Liver Diseases University of Miami School of Medicine Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Bowlus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology UC Davis School of Medicine Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Lawitz","sequence":"additional","affiliation":[{"name":"The Texas Liver Institute University of Texas Health San Antonio Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuno","family":"Antunes","sequence":"additional","affiliation":[{"name":"Ipsen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Miller","sequence":"additional","affiliation":[{"name":"Ipsen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfen","family":"Shu","sequence":"additional","affiliation":[{"name":"Ipsen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia O.","family":"Zein","sequence":"additional","affiliation":[{"name":"Ipsen Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris V.","family":"Kowdley","sequence":"additional","affiliation":[{"name":"Liver Institute Northwest Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,6]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.022"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30145"},{"key":"e_1_2_14_4_1","first-page":"5","article-title":"An Examination of the Evidence Behind Biochemical Markers in Primary Biliary Cholangitis","volume":"17","author":"Kowdley K. V.","year":"2021","journal-title":"Gastroenterology & Hepatology (N Y)"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.029"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000557"},{"key":"e_1_2_14_7_1","unstructured":"EMA Reflection Paper on Regulatory Requirements for the Development of Medicinal Products for Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC)(2023) accessed March 2026 https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/reflection\u2010paper\u2010regulatory\u2010requirements\u2010development\u2010medicinal\u2010products\u2010primary\u2010biliary\u2010cholangitis\u2010pbc\u2010primary\u2010sclerosing\u2010cholangitis\u2010psc_en.pdf."},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1180"},{"key":"e_1_2_14_9_1","unstructured":"FDA \u201cIQIRVO Highlights of Prescribing Information \u201d(2024) accessed July 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/218860s000lbl.pdf."},{"key":"e_1_2_14_10_1","unstructured":"EMA \u201cIQIRVO Elafibranor \u201daccessed July 2025 https:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\u2010overview\/marketing\u2010authorisation\/conditional\u2010marketing\u2010authorisation."},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2306185"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714519"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312100"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000001465"},{"key":"e_1_2_14_15_1","unstructured":"FDA.\u201cLIVDELZI (Seladelpar) Integrated Review \u201d(2023):38 accessed August 2025 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2024\/217899Orig1s000IntegratedR.pdf."},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2017.06.006"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjgast-2020-000502"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000864"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70630","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70630","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70630","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:16:04Z","timestamp":1783426564000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70630"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,6]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/liv.70630"],"URL":"https:\/\/doi.org\/10.1111\/liv.70630","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,6]]},"assertion":[{"value":"2025-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70630"}}