{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:14:24Z","timestamp":1768000464847,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2021,4,10]],"date-time":"2021-04-10T00:00:00Z","timestamp":1618012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Chaim Sheba Medical Center"},{"DOI":"10.13039\/100007028","name":"Leona M. and Harry B. Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PDE\/BDE\/114583\/2016"],"award-info":[{"award-number":["PDE\/BDE\/114583\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Real life data regarding pharmacokinetics of vedolizumab in patients needing dose optimisation are scarce. We set to examine whether pre-optimisation vedolizumab levels associate with therapy outcomes and which mechanisms explain the associations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A multicentre observational study assessed the outcome of dose increase in association with pre-escalation levels in vedolizumab-treated patients. SubsequentIy, \u03b14\u03b27 occupancy on peripheral blood [PB] and intestinal lamina propria [LP] tissues was investigated on various cellular subsets in patients undergoing lower endoscopy on infusion day. Cellular localisation of vedolizumab-bound \u03b14\u03b27 and effects on M1 and M2 macrophages were also explored.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 161 inflammatory bowel disease [IBD] patients were included. Among 129\/161 patients intensified during maintenance [Week 14 onward], pre-intensification trough levels were comparable or higher among those subsequently attaining post-optimisation clinical, biomarker, and endoscopic remission, compared with non-remitting patients [p\u2005=\u20050.09, 0.25, 0.04, respectively]. Similar results were demonstrated for those dose-optimised during induction [Week 6, n\u2005=\u200532]. In the immune sub-study [n\u2005=\u200543], free \u03b14\u03b27 receptors at trough were similarly low among patients with\/without mucosal healing, on PB T cells [p\u2005=\u20050.15], LP T cells [p\u2005=\u20050.88], and on PB eosinophils [p\u2005=\u20050.08]. Integrin receptors on M1 and M2 macrophages were also saturated by low levels of vedolizumab and anti-inflammatory cytokine secretion was not increased. Co-localisation and dissociation experiments demonstrated membranal \u03b14\u03b27 receptors of two origins: non-internalised and newly generated \u03b14\u03b27, but re-binding was still complete at very low concentrations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results do not support pharmacokinetics as the mechanism responsible for loss of response to vedolizumab, nor do they support a need for higher drug concentration to enhance vedolizumab\u2019s immune effects. Higher pre-escalation levels may indicate less clearance [less severe disease] and higher likelihood of subsequent re-gained response, regardless of therapy escalation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjab067","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T21:39:38Z","timestamp":1617917978000},"page":"1707-1719","source":"Crossref","is-referenced-by-count":28,"title":["Dose optimisation for Loss of Response to Vedolizumab\u2014 Pharmacokinetics and Immune Mechanisms"],"prefix":"10.1093","volume":"15","author":[{"given":"Bella","family":"Ungar","sequence":"first","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}]},{"given":"Karin","family":"Malickova","sequence":"additional","affiliation":[{"name":"IBD Clinical and Research Centre, ISCARE, Prague, Czech 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Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7225-9765","authenticated-orcid":false,"given":"Zohar","family":"Ben Shatach","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}]},{"given":"Chaya Mushka","family":"Abitbol","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}]},{"given":"Ola","family":"Haj Natour","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}]},{"given":"Limor","family":"Selinger","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, 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Aviv University, Tel Aviv, Israel"}]},{"given":"Uri","family":"Kopylov","sequence":"additional","affiliation":[{"name":"Gastroenterology Institute, Sheba Medical Center Tel Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}]},{"given":"Fernando","family":"Magro","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Xavier","family":"Roblin","sequence":"additional","affiliation":[{"name":"Department of Hepatogastroenterology, University Hospital of Saint Etienne, Saint Etienne, France"}]},{"given":"Yehuda","family":"Chowers","sequence":"additional","affiliation":[{"name":"Rambam Health Care Campus, Bruce and Ruth Rappaport Faculty of Medicine, Haifa, Israel"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2734-675X","authenticated-orcid":false,"given":"David","family":"Drobne","sequence":"additional","affiliation":[{"name":"Department 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