{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:11:20Z","timestamp":1791652280481,"version":"4.3.4"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"crossref","award":["6777"],"award-info":[{"award-number":["6777"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Ulcerative colitis (UC) and Crohn\u2019s disease (CD) differ in intestinal location and depth of involvement. Patients with UC who have or experienced a flare-up according to Truelove\u2013Witts criteria (ACUS), as well as those with fistulizing Crohn\u2019s disease (FIST), may represent difficult-to-treat populations. This study investigates the phenotype- and severity-driven selection of infliximab (IFX) population pharmacokinetic models to optimize predictive performance and support precision dosing in inflammatory bowel disease (IBD) care. A retrospective analysis was conducted at University Hospital Medical Centre \u201cZvezdara\u201d. Twenty published IFX models were evaluated across five datasets (overall, ASUC, CD, FIST, UC), primarily using trough concentrations obtained via routine therapeutic drug monitoring. Predictive accuracy was assessed using median prediction error (MDPE) and median absolute prediction error (MAPE). Bayesian forecasts were evaluated using median individual prediction error (MDIPE) and its absolute value (MAIPE). Normalized prediction distribution errors (NPDE) and visual predictive check (VPC) were used for simulation-based diagnostics. Moreover, probability of probability of target-attainment (PTA%) per model and subgroup was calculated. No model met all predefined prediction-based performance criteria. In\n                    <jats:italic>a priori<\/jats:italic>\n                    analysis, the Matsuoka model showed the satisfactory overall performance, while the Xu model was most suitable for CD patients. In\n                    <jats:italic>a posteriori<\/jats:italic>\n                    analysis, the Ternant 2008 model had the well overall accuracy, with other models (Dreesen 2021 for ASUC, Matsuoka for CD, Brandse 2016 for UC) performing satisfactory in respective subgroups. Simulation NPDE diagnostics identified the Aubourg model as suitable for the overall dataset, while VPC results mainly supported the\n                    <jats:italic>a priori<\/jats:italic>\n                    analysis conclusions. These findings highlight the relevance of disease phenotype and severity in selecting IFX pharmacokinetic models. Rather than relying on a one-size-fits-all approach, tailoring model choice to patient subgroups enhances predictive performance. This supports a more individualized, model-informed precision dosing (MIPD) strategy for optimizing IFX dosing in IBD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352967","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:43:14Z","timestamp":1784914994000},"page":"e0352967","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic model selection for infliximab based on inflammatory bowel disease phenotype and severity: Toward model-informed precision dosing"],"prefix":"10.1371","volume":"21","author":[{"given":"Ana","family":"Hom\u0161ek Ili\u0107","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Jovanovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sr\u0111an","family":"Markovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Vezmar Kova\u010devi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Kne\u017eevi\u0107 Ivanovski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0110or\u0111e","family":"Kralj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Svorcan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9676-5785","authenticated-orcid":true,"given":"Katarina","family":"Vu\u010di\u0107evi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"pone.0352967.ref001","article-title":"Inflammatory Bowel Disease","volume-title":"StatPearls","author":"C McDowell","year":"2023"},{"key":"pone.0352967.ref002","first-page":"196","article-title":"Inflammatory bowel disease","volume-title":"Clinical pharmacy & therapeutics","author":"S Cripps","year":"2019","edition":"6"},{"key":"pone.0352967.ref003","first-page":"552","article-title":"Ulcerative colitis.","volume-title":"Encyclopedia of gastroenterology","author":"SD Lee","year":"2020","edition":"2"},{"key":"pone.0352967.ref004","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-323-67293-1.00042-6","article-title":"Crohn Disease","author":"JL Dotson","year":"2021","journal-title":"Pediatric Gastrointestinal and Liver Disease"},{"key":"pone.0352967.ref005","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1136\/bmj.2.4884.375","article-title":"Cortisone in ulcerative colitis","volume":"2","author":"SC Truelove","year":"1954","journal-title":"Br Med J"},{"issue":"1","key":"pone.0352967.ref006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cgh.2006.09.033","article-title":"Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression","volume":"5","author":"D Turner","year":"2007","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"1","key":"pone.0352967.ref007","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S2468-1253(16)30003-6","article-title":"Infliximab versus ciclosporin for steroid-resistant acute severe ulcerative colitis (CONSTRUCT): a mixed methods, open-label, pragmatic randomised trial","volume":"1","author":"JG Williams","year":"2016","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"2","key":"pone.0352967.ref008","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1136\/gutjnl-2016-313060","article-title":"Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab","volume":"67","author":"D Laharie","year":"2018","journal-title":"Gut"},{"issue":"5","key":"pone.0352967.ref009","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.gastro.2003.08.025","article-title":"AGA technical review on perianal Crohn\u2019s 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