{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:21:44Z","timestamp":1790288504336,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004330","name":"GSK","doi-asserted-by":"publisher","award":["201000"],"award-info":[{"award-number":["201000"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Total serum bile acid (TSBA) levels are elevated in patients with primary biliary cholangitis (PBC) and may mediate cholestatic pruritus. Linerixibat, an ileal bile acid transporter inhibitor, improved pruritus in patients with PBC. We explored the relationship between linerixibat dose, TSBA concentration, and pruritus.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data from Phase 1\/2 trials were used to develop a population kinetic\u2010pharmacodynamic model to characterize the linerixibat dose\u2013TSBA relationship. Individual Bayesian parameter estimates for participants in the GLIMMER study were used to derive the area under the TSBA concentration curve over 24\u2009h (AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      ). Time\u2010matched post hoc estimates of AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      were correlated with pruritus reported on a 0\u201310 numerical rating scale. Baseline TSBA concentration was correlated with change from baseline (\u0394BL) in monthly itch score (MIS). \u0394BL in model\u2010estimated TSBA AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      was correlated with time\u2010matched \u0394BL in weekly itch score (WIS) or MIS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Linerixibat dose dependently reduced TSBA AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      , reaching steady state after 5\u2009days. Baseline TSBA levels in GLIMMER did not correlate with \u0394BL in MIS. \u0394BL in TSBA AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      correlated with improved WIS over 12\u2009weeks of treatment (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.52,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Of participants with a\u2009\u226530% decrease in TSBA AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      , 60% were pruritus responders (\u22652\u2010point improvement in WIS from baseline).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Linerixibat treatment leads to rapid, dose\u2010dependent TSBA reductions. Baseline TSBA levels do not correlate with on\u2010treatment pruritus change, suggesting they do not predict linerixibat response. Change in TSBA AUC\n                      <jats:sub>0\u201324<\/jats:sub>\n                      correlates significantly with, and can be predictive of, pruritus improvement in patients with PBC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.15982","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T07:55:04Z","timestamp":1716450904000},"page":"2293-2302","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat"],"prefix":"10.1111","volume":"44","author":[{"given":"Eleni","family":"Karatza","sequence":"first","affiliation":[{"name":"The University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4179-4842","authenticated-orcid":false,"given":"Brandon","family":"Swift","sequence":"additional","affiliation":[{"name":"GSK  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Carre\u00f1o","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumanta","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Casillas","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-7172","authenticated-orcid":false,"given":"Janelle","family":"Lennie","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Fettiplace","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9263-948X","authenticated-orcid":false,"given":"Andreas E.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospital Zurich, University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.12.007"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-022-07581-x"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfma.2016.05.006"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.01.037"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26365"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i19.3418"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30145"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i25.7683"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.4.5946.693"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00931"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30319-7"},{"key":"e_1_2_13_13_1","unstructured":"US Food and Drug Administration.Highlights of prescribing information (Bylvay [odevixibat]).2021. 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