{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:52:27Z","timestamp":1790113947036,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018353","name":"European Crohn's and Colitis Organisation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018353","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008373","name":"Takeda Pharmaceutical Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008373","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":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To define the exposure\u2013response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C\u2010reactive protein [CRP]\/erythrocyte sedimentation rate [ESR] and steroid\u2010free remission) at 30\u2009weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior. We employed the model for exposure\u2013response evaluation and for investigating doses in paediatric patients to match the adult exposure at the labelled dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At Week 30, 104\/129 (81%) children (53% female and 47% Crohn disease) remained on vedolizumab, of whom 39 (31%) in the exposure\u2010response evaluation were in deep biochemical remission. Increased baseline drug clearance was associated with lower deep biochemical remission rates at Week 30 based on ESR\/CRP (OR 0.47 [95% CI 0.2\u20131.05,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.08]) and calprotectin &lt;\u2009100\u2009\u03bcg\/g (OR 0.13 [95% CI 0.1\u20130.79,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05]). Higher weight and lower serum albumin were associated with increased clearance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Simulation models found that, for children \u2264\u200930\u2009kg, tiered fixed dosing regimens best matched adult drug concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Drug clearance was strongly influenced by serum albumin. Baseline clearance predicted deep biochemical remission at Week 30. Further investigation is needed to better understand optimal dosing strategies\u2014especially for lower\u2010weight children receiving vedolizumab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.18484","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T09:49:12Z","timestamp":1736934552000},"page":"1000-1010","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the\n                    <scp>VedoKids<\/scp>\n                    Prospective Multicentre Study"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4494-2388","authenticated-orcid":false,"given":"Ronen","family":"Stein","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5160-868X","authenticated-orcid":false,"given":"Dan","family":"Turner","sequence":"additional","affiliation":[{"name":"The Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&amp;D Authority, Shaare Zedek Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9362-0465","authenticated-orcid":false,"given":"S\u00e9amus","family":"Hussey","sequence":"additional","affiliation":[{"name":"National Children's Research Center University College Dublin and Royal College of Surgeons of Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysha","family":"Kawasmi","sequence":"additional","affiliation":[{"name":"The Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&amp;D Authority, Shaare Zedek Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oren","family":"Ledder","sequence":"additional","affiliation":[{"name":"The Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&amp;D Authority, Shaare Zedek Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremiah","family":"Levine","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology and Hepatology New York University Langone Health  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Markowitz","sequence":"additional","affiliation":[{"name":"The Feinstein Institute for Medical Research, Northwell  Manhasset New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Matar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition Schneider Children's Medical Center of Israel  Petah Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Orlanski\u2010Meyer","sequence":"additional","affiliation":[{"name":"The Juliet Keidan Institute of Pediatric Gastroenterology, The Eisenberg R&amp;D Authority, Shaare Zedek Medical Center The Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K.","family":"Russell","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology The Royal Hospital for Children &amp; Young People  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron","family":"Shaoul","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Institute, Ruth Rappaport Children's Hospital, Rambam Medical Center, Faculty of Medicine, Technion  Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anat","family":"Yerushalmy\u2010Feler","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology Institute Dana\u2010Dwek Children's Hospital, Tel Aviv Sourasky Medical Center  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane R.","family":"Mould","sequence":"additional","affiliation":[{"name":"Projections Research  Phoenixville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maire A.","family":"Conrad","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics The Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002631"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15484"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030972"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16937"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjac036"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(22)00307-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21649"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.05.029"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01061030"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1012299115260"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-006-9043-z"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12422"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13243"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/psp.2013.14"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-007-9081-1"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","unstructured":"K.Yoshida \u201crstanemax: Emax Model Analysis With \u2018Stan\u2019 \u201d R Package Version 0.1.3 (2020) https:\/\/CRAN.R\u2010project.org\/package=rstanemax.","DOI":"10.32614\/CRAN.package.rstanemax"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-21706-2"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"e_1_2_9_20_1","unstructured":"D.Robinson \u201cbroom: Convert Statistical Analysis Objects Into Tidy Data Frames \u201d R Package Version 0.4.2 (2017) https:\/\/CRAN.R\u2010project.org\/package=broom."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v033.i01"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","unstructured":"A.KassambaraandM.Kosinski \u201csurvminer: Drawing Survival Curves Using \u2018ggplot2\u2019 \u201d R package Version 0.4.0 (2017) https:\/\/CRAN.R\u2010project.org\/package=survminer.","DOI":"10.32614\/CRAN.package.survminer"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-022-07783-3"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17277"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002536"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2021.1977843"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000137"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000769"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020888"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-13-36"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-017-0082-8"},{"key":"e_1_2_9_32_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration \u201cLeveraging Existing Clinical Data for Extrapolation to Pediatric Uses of Medical Devices: Guidance for Industry and Food and Drug Administrative Staff \u201d Updated June 21 2016 accessed February 16 2024 https:\/\/www.fda.gov\/media\/91889\/download."},{"key":"e_1_2_9_33_1","unstructured":"U.S. Department of Health and Human Services Food and Drug Administration \u201cE11A Pediatric Extrapolation \u201d Updated April 4 2022 accessed February 16 2024 https:\/\/www.fda.gov\/media\/161190\/download."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.10.005"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2023.11.004"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.03.072"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2189"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izz143"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab285"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.18484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T19:58:47Z","timestamp":1741723127000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.18484"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,15]]},"references-count":38,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1111\/apt.18484"],"URL":"https:\/\/doi.org\/10.1111\/apt.18484","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,15]]},"assertion":[{"value":"2024-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}