{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:21:03Z","timestamp":1790673663318,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp; Syst Pharma"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Infliximab dosage de\u2010escalation without prior knowledge of drug concentrations may put patients at risk for underexposure and trigger the loss of response. A single\u2010model approach for model\u2010informed precision dosing during infliximab maintenance therapy has proven its clinical benefit in patients with inflammatory bowel diseases. We evaluated the predictive performances of two multi\u2010model approaches, a model selection algorithm and a model averaging algorithm, using 18 published population pharmacokinetic models of infliximab for guiding dosage de\u2010escalation. Data of 54 patients with Crohn\u2019s disease and ulcerative colitis who underwent infliximab dosage de\u2010escalation after an earlier escalation were used. A priori prediction (based solely on covariate data) and maximum a posteriori prediction (based on covariate data and trough concentrations) were compared using accuracy and precision metrics and the classification accuracy at the trough concentration target of 5.0\u2009mg\/L. A priori prediction was inaccurate and imprecise, with the lowest classification accuracies irrespective of the approach (median 59%, interquartile range 59%\u201363%). Using the maximum a posteriori prediction, the model averaging algorithm had systematically better predictive performance than the model selection algorithm or the single\u2010model approach with any model, regardless of the number of concentration data. Only a single trough concentration (preferably at the point of care) sufficed for accurate and precise prediction. Predictive performance of both single\u2010 and multi\u2010model approaches was robust to the lack of covariate data. Model averaging using four models demonstrated similar predictive performance with a five\u2010fold shorter computation time. This model averaging algorithm was implemented in the TDMx software tool to guide infliximab dosage de\u2010escalation in the forthcoming prospective MODIFI study (NCT04982172).<\/jats:p>","DOI":"10.1002\/psp4.12813","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T01:40:00Z","timestamp":1655343600000},"page":"1045-1059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Multi\u2010model averaging improves the performance of model\u2010guided infliximab dosing in patients with inflammatory bowel diseases"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9285-799X","authenticated-orcid":false,"given":"Wannee","family":"Kantasiripitak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7351-0023","authenticated-orcid":false,"given":"An","family":"Outtier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Chronic Diseases and Metabolism University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-4845","authenticated-orcid":false,"given":"Sebastian G.","family":"Wicha","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Institute of Pharmacy University of Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5295-010X","authenticated-orcid":false,"given":"Alexander","family":"Kensert","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Leuven  Leuven Belgium"},{"name":"Department of Chemical Engineering Vrije Universiteit Brussels  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6415-2044","authenticated-orcid":false,"given":"Zhigang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8892-7075","authenticated-orcid":false,"given":"Jo\u00e3o","family":"Sabino","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Chronic Diseases and Metabolism University of Leuven  Leuven 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University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Chronic Diseases and Metabolism University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0785-2930","authenticated-orcid":false,"given":"Erwin","family":"Dreesen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31711-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32126-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2011.04612.x"},{"key":"e_1_2_9_5_1","first-page":"139","article-title":"Remicade\u00ae (infliximab): 20\u2009years of contributions to science and 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