{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:51:44Z","timestamp":1790095904392,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:00:00Z","timestamp":1720483200000},"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":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>Upadacitinib, a selective Janus kinase inhibitor, is the first orally administered therapy approved for the treatment of Crohn's disease (CD). This work characterized the pharmacokinetics of upadacitinib in CD patients and evaluated the relationships between upadacitinib steady\u2010state plasma exposures and efficacy as well as safety parameters during the 12\u2010week induction and the 52\u2010week maintenance periods, to provide dosing recommendations for the treatment of CD. Upadacitinib pharmacokinetics in CD patients administered the extended\u2010release formulation were consistent with patient populations in other approved indications. None of the evaluated CD\u2010specific patient characteristics (e.g., disease location and prior gastrointestinal surgeries) had a meaningful impact on upadacitinib pharmacokinetics. Exposure\u2013response analyses during 12\u2010week induction treatment showed that response across all evaluated efficacy end points were approaching a plateau at median plasma exposures associated with 45\u2009mg QD. Analyses for the maintenance period demonstrated that 30\u2009mg QD is predicted to provide an additional 8% to 10% benefit for endoscopic response and endoscopic remission compared with 15\u2009mg QD in patients who failed biologics. The analyses for safety showed a statistically significant relationship between increasing upadacitinib plasma exposures and the percentage of patients experiencing &gt;2\u2009g\/dL decrease in hemoglobin from Baseline during induction and showed shallow relationships for serious infections and herpes zoster during the maintenance period. These results demonstrated adequate absorption of the extended\u2010release formulation of upadacitinib in CD patients. The exposure\u2013response analyses confirmed that 45\u2009mg QD dose maximized efficacy as induction treatment and supported the selection of 15\u2009mg QD or 30\u2009mg QD as the maintenance doses.<\/jats:p>","DOI":"10.1002\/cpt.3359","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T03:54:50Z","timestamp":1720583690000},"page":"1240-1251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacokinetics and Exposure\u2013Response Analyses to Support Dose Selection of Upadacitinib in Crohn's Disease"],"prefix":"10.1002","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4410-8131","authenticated-orcid":false,"given":"Sumit","family":"Bhatnagar","sequence":"first","affiliation":[{"name":"Clinical Pharmacology AbbVie  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5822-4246","authenticated-orcid":false,"given":"Louisa","family":"Schlachter","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology AbbVie Deutschland GmbH &amp; Co. 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