{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:29:17Z","timestamp":1792384157824,"version":"4.4.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T00:00:00Z","timestamp":1517184000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double\u2010blind, placebo\u2010controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3\u00a0months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double\u2010blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3\/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6\u2010year open\u2010label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg \u221253.9% [\u221262.5, \u221229.3], OCA 50 mg \u221237.2% [\u221254.8, \u221224.6]) compared to placebo (\u22120.8% [\u22126.4, 8.7];\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001) at the end of the study, with similar reductions observed through 6\u00a0years of open\u2010label extension treatment. OCA improved many secondary and exploratory endpoints (including \u03b3\u2010glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long\u2010term clinical outcomes. Pruritus increased dose\u2010dependently with OCA treatment. Biochemical improvements were observed through 6 years of open\u2010label extension treatment. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2018;67:1890\u20101902).\n                  <\/jats:p>","DOI":"10.1002\/hep.29569","type":"journal-article","created":{"date-parts":[[2017,10,10]],"date-time":"2017-10-10T14:57:08Z","timestamp":1507647428000},"page":"1890-1902","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":265,"title":["A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis"],"prefix":"10.1097","volume":"67","author":[{"given":"Kris V.","family":"Kowdley","sequence":"first","affiliation":[{"name":"Liver Care Network,Swedish Medical Center,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velimir","family":"Luketic","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University and McGuire Research Institute,McGuire DVAMC,Richmond,VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Chapman","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, John Radcliffe Hospital,Headington,Oxford,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Centre for Liver Research and NIHR Biomedical Research Centre,University of Birmingham,Birmingham,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raoul","family":"Poupon","sequence":"additional","affiliation":[{"name":"H\u00f4pital Saint\u2010Antoine, AP\u2010HdP,Paris,France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schramm","sequence":"additional","affiliation":[{"name":"1st Department of Medicine,University Medical Center Hamburg\u2010Eppendorf,Hamburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vincent","sequence":"additional","affiliation":[{"name":"Liver Unit,H\u00f4pital Saint\u2010Luc,Montr\u00e9al,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Rust","sequence":"additional","affiliation":[{"name":"Department of Medicine 2, Grosshadern,University of Munich,Munich,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Par\u00e9s","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital Clinic, IDIBAPS, CIBERehd,University of Barcelona,Barcelona,Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,University of Alberta,Edmonton,Alberta,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns\u2010Ulrich","family":"Marschall","sequence":"additional","affiliation":[{"name":"Sahlgrenska Academy,Department of Molecular and Clinical Medicine, University of Gothenburg,Gothenburg,Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Adorini","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathi","family":"Sciacca","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Beecher\u2010Jones","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"B\u00f6hm","sequence":"additional","affiliation":[{"name":"FGK Clinical Research,Munich,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Pencek","sequence":"additional","affiliation":[{"name":"Intercept Pharmaceuticals Inc.,San Diego,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Jones","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine,Newcastle University,Newcastle\u2010upon\u2010Tyne,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Obeticholic Acid PBC Monotherapy Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,1,29]]},"reference":[{"key":"hep29569-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-pathol-020712-164014","article-title":"The immunobiology and pathophysiology of primary biliary cirrhosis","volume":"8","year":"2013","journal-title":"Annu Rev Pathol"},{"key":"hep29569-bib-0002-20241017","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/hep.28140","article-title":"Changing nomenclature for PBC: from \u201ccirrhosis\u201d to \u201ccholangitis","volume":"62","year":"2015","journal-title":"Hepatology"},{"key":"hep29569-bib-0003-20241017","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jhep.2009.04.009","article-title":"EASL clinical practice guidelines: management of cholestatic liver diseases","volume":"51","year":"2009","journal-title":"J Hepatol"},{"key":"hep29569-bib-0004-20241017","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/hep.22906","article-title":"Primary biliary cirrhosis: AASLD practice guidelines","volume":"50","year":"2009","journal-title":"Hepatology"},{"key":"hep29569-bib-0005-20241017","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/S1665-2681(19)30838-5","article-title":"Predicting outcome in primary biliary cirrhosis","volume":"13","year":"2014","journal-title":"Ann Hepatol"},{"key":"hep29569-bib-0006-20241017","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.jhep.2011.02.031","article-title":"Early primary biliary cirrhosis: biochemical response to treatment and prediction of long\u2010term outcome","volume":"55","year":"2011","journal-title":"J Hepatol"},{"key":"hep29569-bib-0007-20241017","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","article-title":"Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow\u2010up study","volume":"147","year":"2014","journal-title":"Gastroenterology"},{"key":"hep29569-bib-0008-20241017","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid","volume":"148","year":"2015","journal-title":"Gastroenterology"},{"key":"hep29569-bib-0009-20241017","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1046\/j.1365-2036.2003.01792.x","article-title":"Systematic review: ursodeoxycholic acid\u2014adverse effects and drug interactions","volume":"18","year":"2003","journal-title":"Aliment Pharmacol Ther"},{"key":"hep29569-bib-0010-20241017","doi-asserted-by":"crossref","first-page":"3569","DOI":"10.1021\/jm025529g","article-title":"6Alpha\u2010ethyl\u2010chenodeoxycholic acid (6\u2010ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity","volume":"45","year":"2002","journal-title":"J Med Chem"},{"key":"hep29569-bib-0011-20241017","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of bile acids and bile acid receptors in metabolic regulation","volume":"89","year":"2009","journal-title":"Physiol Rev"},{"key":"hep29569-bib-0012-20241017","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000371670","article-title":"Bile acids as hormones: the FXR\u2010FGF15\/19 pathway","volume":"33","year":"2015","journal-title":"Dig Dis"},{"issue":"Suppl.","key":"hep29569-bib-0013-20241017","first-page":"S25","article-title":"New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond","volume":"62","year":"2015","journal-title":"J Hepatol"},{"key":"hep29569-bib-0014-20241017","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1053\/j.gastro.2004.08.001","article-title":"The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liver fibrosis","volume":"127","year":"2004","journal-title":"Gastroenterology"},{"key":"hep29569-bib-0015-20241017","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo\u2010controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","year":"2016","journal-title":"N Engl J Med"},{"key":"hep29569-bib-0016-20241017","first-page":"930","article-title":"The UK\u2010PBC risk scores: derivation and validation of a scoring system for long\u2010term prediction of end\u2010stage liver disease in primary biliary cirrhosis","volume":"63","year":"2015","journal-title":"Hepatology"},{"key":"hep29569-bib-0017-20241017","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1053\/j.gastro.2015.07.061","article-title":"Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy","volume":"149","year":"2015","journal-title":"Gastroenterology"},{"key":"hep29569-bib-0018-20241017","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1002\/sim.1300","article-title":"Combined endpoints: can we use them?","volume":"21","year":"2002","journal-title":"Stat Med"},{"key":"hep29569-bib-0019-20241017","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1016\/S0168-8278(99)80136-6","article-title":"Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial","volume":"30","year":"1999","journal-title":"J Hepatol"},{"key":"hep29569-bib-0020-20241017","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1056\/NEJM199105303242204","article-title":"A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA\u2010PBC Study Group","volume":"324","year":"1991","journal-title":"N Engl J Med"},{"key":"hep29569-bib-0021-20241017","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1016\/0016-5085(94)90021-3","article-title":"Ursodeoxycholic acid in the treatment of primary biliary cirrhosis","volume":"106","year":"1994","journal-title":"Gastroenterology"},{"key":"hep29569-bib-0022-20241017","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1002\/hep.1840190512","article-title":"The Canadian Multicenter Double\u2010blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis","volume":"19","year":"1994","journal-title":"Hepatology"},{"key":"hep29569-bib-0023-20241017","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0168-8278(00)80216-0","article-title":"Long\u2010term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double\u2010blind controlled multicentric trial. UDCA\u2010Cooperative Group from the Spanish Association for the Study of the Liver","volume":"32","year":"2000","journal-title":"J Hepatol"},{"key":"hep29569-bib-0024-20241017","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1159\/000341420","article-title":"Combined rifampicin and ursodeoxycholic acid treatment does not amplify rifampicin effects on hepatic detoxification and transport systems in humans","volume":"86","year":"2012","journal-title":"Digestion"},{"key":"hep29569-bib-0025-20241017","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.jaut.2010.09.005","article-title":"PBC screen: an IgG\/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis","volume":"35","year":"2010","journal-title":"J Autoimmun"},{"key":"hep29569-bib-0026-20241017","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jaut.2015.07.004","article-title":"The immunogenetics of primary biliary cirrhosis: a comprehensive review","volume":"64","year":"2015","journal-title":"J Autoimmun"},{"key":"hep29569-bib-0027-20241017","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jaut.2011.11.005","article-title":"Primary biliary cirrhosis and Sjogren's syndrome: autoimmune epithelitis","volume":"39","year":"2012","journal-title":"J Autoimmun"},{"key":"hep29569-bib-0028-20241017","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1002\/hep.27715","article-title":"Liver alkaline phosphatase: a missing link between choleresis and biliary inflammation","volume":"61","year":"2015","journal-title":"Hepatology"},{"key":"hep29569-bib-0029-20241017","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1542-3565(03)00134-4","article-title":"Natural history of pruritus in primary biliary cirrhosis","volume":"1","year":"2003","journal-title":"Clin Gastroenterol Hepatol"},{"key":"hep29569-bib-0030-20241017","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(15)00154-3","article-title":"Primary biliary cirrhosis","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"hep29569-bib-0031-20241017","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.atherosclerosis.2006.11.036","article-title":"Primary biliary cirrhosis, hyperlipidemia, and atherosclerotic risk: a systematic review","volume":"194","year":"2007","journal-title":"Atherosclerosis"},{"key":"hep29569-bib-0032-20241017","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.atherosclerosis.2010.09.016","article-title":"Upregulation of scavenger receptor class B type I expression by activation of FXR in hepatocyte","volume":"213","year":"2010","journal-title":"Atherosclerosis"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.29569","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep.29569","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep.29569","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-201805000-00029","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T20:10:58Z","timestamp":1729195858000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-201805000-00029"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,29]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.29569","relation":{},"ISSN":["0270-9139","1527-3350"],"issn-type":[{"value":"0270-9139","type":"print"},{"value":"1527-3350","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,29]]},"assertion":[{"value":"2017-04-21","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}