{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T02:07:42Z","timestamp":1767924462759,"version":"3.49.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Portuguese Study Group in Inflammatory Bowel Disease"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and aims<\/jats:title>\n                  <jats:p>Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study\u2019s primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjae014","type":"journal-article","created":{"date-parts":[[2024,1,20]],"date-time":"2024-01-20T14:45:53Z","timestamp":1705761953000},"page":"1102-1112","source":"Crossref","is-referenced-by-count":4,"title":["The Influence of Subclinical Active Inflammation on IFX Pharmacokinetic Modeling and Disease Progression Assessment: Findings from a Prospective Real-World Study in Inflammatory Bowel Disease Patients"],"prefix":"10.1093","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2634-9668","authenticated-orcid":false,"given":"Fernando","family":"Magro","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto , Porto , Portugal"},{"name":"Department of Gastroenterology, S\u00e3o Jo\u00e3o Hospital University Centre , Porto , Portugal"},{"name":"Centre for Health Technology and Services Research, Health Research Network (CINTESIS@RISE), Faculty of Medicine of the University of Porto , Portugal"},{"name":"Clinical Pharmacology Unit, S\u00e3o Jo\u00e3o Hospital University Centre , Porto , Portugal"},{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , Portugal"}]},{"given":"Samuel","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Northern Lisbon University Hospital Centre , Lisbon , Portugal"},{"name":"Clinica Universit\u00e1ria de Gastrenterologia da Universidade de Medicina de Lisboa , Lisbon , Portugal"}]},{"given":"Marta","family":"Patita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Garcia da Orta Hospital , Almada , Portugal"}]},{"given":"Bruno","family":"Arroja","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Braga Hospital , Braga , Portugal"}]},{"given":"Paula","family":"Lago","sequence":"additional","affiliation":[{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , Portugal"},{"name":"Department of Gastroenterology, Porto Hospital University Centre , Porto , Portugal"}]},{"given":"Isadora","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, IPOLFG, EPE , Lisbon , Portugal"}]},{"given":"Helena","family":"Tavares de Sousa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Algarve Hospital University Centre - Portim\u00e3o Unit , Portim\u00e3o , Portugal"},{"name":"ABC \u2013 Algarve Biomedical Center, University of Algarve , Faro , Portugal"}]},{"given":"Paula","family":"Ministro","sequence":"additional","affiliation":[{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , Portugal"},{"name":"Department of Gastroenterology, Viseu-Tondela Hospital Centre , Viseu , Portugal"}]},{"given":"Irina","family":"Mocanu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Garcia da Orta Hospital , Almada , Portugal"}]},{"given":"Ana","family":"Vieira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Garcia da Orta Hospital , Almada , Portugal"}]},{"given":"Joana","family":"Castela","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, IPOLFG, EPE , Lisbon , Portugal"}]},{"given":"Joana","family":"Moleiro","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, IPOLFG, EPE , Lisbon , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5098-8729","authenticated-orcid":false,"given":"Joana","family":"Roseira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Algarve Hospital University Centre - Portim\u00e3o Unit , Portim\u00e3o , Portugal"},{"name":"ABC \u2013 Algarve Biomedical Center, University of Algarve , Faro , Portugal"}]},{"given":"Eug\u00e9nia","family":"Cancela","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Viseu-Tondela Hospital Centre , Viseu , Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-9635","authenticated-orcid":false,"given":"Paula","family":"Sousa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Viseu-Tondela Hospital Centre , Viseu , Portugal"}]},{"given":"Francisco","family":"Portela","sequence":"additional","affiliation":[{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , Portugal"},{"name":"Department of Gastroenterology, Coimbra Hospital University Centre , Coimbra , Portugal"}]},{"given":"Lu\u00eds","family":"Correia","sequence":"additional","affiliation":[{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , Portugal"},{"name":"Department of Gastroenterology, Northern Lisbon University Hospital Centre , Lisbon , Portugal"}]},{"given":"Paula","family":"Moreira","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit, S\u00e3o Jo\u00e3o Hospital University Centre , Porto , Portugal"}]},{"given":"Sandra","family":"Dias","sequence":"additional","affiliation":[{"name":"Portuguese Group of Studies in Inflammatory Bowel Disease (Grupo de Estudos da Doen\u00e7a Inflamat\u00f3ria Intestinal - GEDII) , Porto , 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