{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T21:52:45Z","timestamp":1790113965908,"version":"4.0.1"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"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":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mirikizumab is a p19\u2010directed anti\u2010interleukin\u201023 antibody approved for the treatment of adults with moderate\u2010to\u2010severe ulcerative colitis (UC). Here, we report the first data of mirikizumab pharmacokinetics (PK) and exposure\u2013response (E\/R) relationships in pediatric participants (aged 2 to &lt;18\u2009years weighing &gt;10\u2009kg) with moderate\u2010to\u2010severe UC from the phase II, open\u2010label study SHINE\u20101 (NCT04004611). PK parameters were analyzed using a model developed previously in adults with fixed\u2010exponent allometry for body weight. Serum samples collected from 26 participants during the 12\u2010week induction and 40\u2010week maintenance periods of SHINE\u20101 were analyzed. Estimated body weight\u2010adjusted systemic clearance, volume of distribution, and subcutaneous bioavailability were 0.021\u2009L\/h, 0.069\u2009L\/kg, and 49.8%, respectively. Covariate analysis identified no clinically significant covariates other than body weight. In the exposure range studied, E\/R analysis using post hoc grouping by average concentration quartile and comparison of observed change from baseline in modified Mayo Score (MMS) at Week 12 with the adult model prediction revealed no obvious E\/R relationship in clinical response, clinical remission, or endoscopic response, consistent with observations in adults. The E\/R relationship for observed change from baseline in MMS at Week 12 is also similar to the adult model prediction. The PK modeling and E\/R analyses suggested optimal doses of intravenous mirikizumab 300\u2009mg for weight &gt;40\u2009kg, 5\u2009mg\/kg for weight \u226440\u2009kg every 4\u2009weeks (Q4W) during induction, and subcutaneous mirikizumab 200\u2009mg (&gt;40\u2009kg), 100\u2009mg (&gt;20 to \u226440\u2009kg), or 50\u2009mg (\u226420\u2009kg) Q4W during maintenance therapy for pediatric patients with moderate\u2010to\u2010severe UC.<\/jats:p>","DOI":"10.1002\/psp4.13286","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T12:39:32Z","timestamp":1734525572000},"page":"474-485","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mirikizumab pharmacokinetics and exposure\u2013response in pediatric patients with moderate\u2010to\u2010severe ulcerative colitis"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7184-8776","authenticated-orcid":false,"given":"Yuki","family":"Otani","sequence":"first","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5417-3062","authenticated-orcid":false,"given":"Laiyi","family":"Chua","sequence":"additional","affiliation":[{"name":"Eli Lilly Singapore  Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7830-1623","authenticated-orcid":false,"given":"Wendy J.","family":"Komocsar","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8698-0369","authenticated-orcid":false,"given":"Amy","family":"Larkin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1013-0303","authenticated-orcid":false,"given":"Jordan","family":"Johns","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-6805","authenticated-orcid":false,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2020.1697227"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.08.043"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2207940"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-024-05428-3"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.06.081"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000001898"},{"issue":"1","key":"e_1_2_11_8_1","first-page":"S52","article-title":"Model\u2010informed pediatric drug development: application of pharmacometrics to define the right dose for children","volume":"61","author":"Vinks AA","year":"2021","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/11535960-000000000-00000"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596370-000000000-00000"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otab007"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01281-z"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3305"},{"key":"e_1_2_11_14_1","first-page":"303","article-title":"A formula to estimate the approximate surface area if height and weight be known. 1916","volume":"5","author":"Du Bois D","year":"1989","journal-title":"Nutrition"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.744"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jpr3.12073"}],"container-title":["CPT: Pharmacometrics &amp; Systems Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/psp4.13286","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T18:12:24Z","timestamp":1742321544000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/psp4.13286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/psp4.13286"],"URL":"https:\/\/doi.org\/10.1002\/psp4.13286","archive":["Portico"],"relation":{},"ISSN":["2163-8306","2163-8306"],"issn-type":[{"value":"2163-8306","type":"print"},{"value":"2163-8306","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"assertion":[{"value":"2024-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}