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However, conventional MIPD often requires manual simulation and regimen selection, which are time\u2010consuming and demand specialized expertise. Reinforcement learning (RL), in which an agent learns optimal decisions through iterative interactions with an environment, offers a scalable and automated alternative. In this study, we developed a model\u2010informed Deep Q\u2010Network (DQN) to personalize infliximab dosing for patients with Crohn\u2019s disease. The DQN was trained in a simulation environment incorporating a population PK model, inter\u2010individual variability, and assay error. Virtual patients with randomly and independently sampled covariates from log\u2010normal distributions were used to explore dosing strategies at Infusions 1, 3, and 4. Doses ranged from 1 to 10\u2009mg\/kg at Infusion 1 and from 1 to 20\u2009mg\/kg thereafter, with intervals of 4\u201312\u2009weeks. The reward function prioritized achieving trough concentrations of 18\u201326\u2009\u03bcg\/mL before Infusion 3 and 5\u201310\u2009\u03bcg\/mL before Infusions 4 and 5, while penalizing overtreatment and additional infusions. The DQN policy converged after 80,000 episodes, yielding target attainment probabilities (PTAs) of 92.9% and 98.4% at Infusions 4 and 5, respectively, in 1000 virtual patients. High doses (11\u201320\u2009mg\/kg) were selected in only 0.2% of cases. At Infusion 4, 66.8% of patients received an 8\u2010week interval, and 57.3% at Infusion 5. Retrospective real\u2010world validation showed that patients whose actual doses matched DQN recommendations had trough levels significantly closer to target ranges. These findings support the feasibility of using DQN\u2010based agents to enhance and automate infliximab individualized dosing in pediatric populations.<\/jats:p>","DOI":"10.1002\/cpt.70118","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T08:24:08Z","timestamp":1762331048000},"page":"555-563","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Model\u2010Informed Deep Q\u2010Networks to Guide Infliximab Dosing in Pediatric Crohn\u2019s Disease"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-1208","authenticated-orcid":false,"given":"Kei","family":"Irie","sequence":"first","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4223-4211","authenticated-orcid":false,"given":"Phillip","family":"Minar","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-0349","authenticated-orcid":false,"given":"Jack","family":"Reifenberg","sequence":"additional","affiliation":[{"name":"University of Cincinnati School of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan M.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Nationwide Children\u2019s Hospital  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Noe","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Children\u2019s Hospital of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9769-236X","authenticated-orcid":false,"given":"Jeffrey S.","family":"Hyams","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition Connecticut Children\u2019s Medical Center  Hartford Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-9826","authenticated-orcid":false,"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children\u2019s Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjaa161"},{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-023-00895-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002304"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2148"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001204"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izac237"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1777"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12588"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12858"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3356"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-97028-6"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2022.104267"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1270443"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70086"},{"key":"e_1_2_12_15_1","article-title":"Efficacy of early optimization of infliximab guided by therapeutic drug monitoring during induction \u2013 a prospective trial","volume":"11","author":"Garcia K.S.","year":"2023","journal-title":"Biomedicine"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjz162"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14236"},{"key":"e_1_2_12_18_1","unstructured":"Wang Z. 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