{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T05:28:11Z","timestamp":1786426091586,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":26,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011684","name":"Crohn\u2019s and Colitis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011684","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK132408"],"award-info":[{"award-number":["DK132408"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 DK078392"],"award-info":[{"award-number":["P30 DK078392"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Crohn\u2019s disease (CD) patients achieving deep remission, defined as clinical remission with endoscopic healing (EH), have a lower rate of CD-related adverse events. EH can be achieved with anti-tumor necrosis factor (TNF) dose optimizations directed by pharmacokinetic (PK) and pharmacodynamic (PD) biomarkers. The primary aim was to identify PK metrics and PD biomarker cut-points associated with EH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this multicenter, cross-sectional study, we enrolled CD patients (age 1-22 years) who received an anti-TNF biologic (infliximab or adalimumab) for &amp;gt;6 months and underwent ileocolonoscopy. EH was defined as a simple endoscopic score-CD (SES-CD)\u2009&amp;lt;\u20093.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighty-seven patients were enrolled with EH found in 55.2%. Lower levels of novel biomarkers neutrophil CD64, monocyte CD64, and soluble CD64 were associated with EH with cut-points of &amp;lt;4.5 ratio (AUROC 0.76), &amp;lt;44.6 ratio (AUROC 0.67), and &amp;lt;15.9 ng\/mL (AUROC 0.67), respectively. There was no difference in the mean trough concentrations of infliximab or adalimumab between EH and non-EH, but the median infliximab clearance was higher in non-EH (0.26 L\/day) compared to EH (0.21 L\/day, P\u2009=\u2009.02). In our infliximab multivariable model, slower infliximab clearance, lower platelet count, and higher serum albumin were strong predictors for EH (AUC 0.90).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified novel PK and PD cut-points for biomarkers associated with EH, including infliximab clearance and the novel CD64 biomarkers. Furthermore, we developed a multivariable PK and PD model for EH that, following validation, could guide dose escalation (PK failures) or prompt a switch to an alternate advanced therapeutic for PD failures.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/crocol\/otag088","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:21:50Z","timestamp":1785151310000},"source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of pharmacokinetic metrics and pharmacodynamic biomarkers associated with endoscopic healing in pediatric Crohn\u2019s disease patients treated with anti-tumor necrosis factor biologics"],"prefix":"10.1093","volume":"8","author":[{"given":"Courtney","family":"Bartel","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH,","place":["United 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Children\u2019s Hospital Medical Center , Cincinnati, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Lynch","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center , Cincinnati, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Cincinnati School of Medicine, Department of Veterans Affairs , Cincinnati, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S","family":"Hyams","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Digestive Diseases, Hepatology and Nutrition, Connecticut Children\u2019s Medical Center , Hartford, CT,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Boyle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children\u2019s Hospital , Columbus, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-8998","authenticated-orcid":false,"given":"Jacob A","family":"Kurowski","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic , Cleveland, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5534-7891","authenticated-orcid":false,"given":"Shehzad","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Wright State University and Dayton Children\u2019s Hospital , Dayton, OH,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D","family":"Noe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children\u2019s Hospital of Wisconsin , Milwaukee, WI,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Chun","sequence":"additional","affiliation":[{"name":"Esoterix, LabCorp Specialty Lab , Calabasas, CA,","place":["United 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