{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:55:31Z","timestamp":1791561331698,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,11,30]],"date-time":"2019-11-30T00:00:00Z","timestamp":1575072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:p>Exposure\u2013response analyses of upadacitinib (UPA) key efficacy and safety end points (3,685 and 4,577 subjects for efficacy and safety, respectively) using data from phase II and phase III rheumatoid arthritis (RA) studies were conducted to support benefit\u2013risk assessment. Percentage of subjects achieving American College of Rheumatology (ACR)20\/50\/70, disease activity score 28 (C\u2010reactive protein) (DAS28\u2010CRP) \u2264\u00a03.2, and DAS28\u2010CRP &lt;\u00a02.6 increased with increasing UPA plasma exposures. With the small number of observed safety events, no clear trends for exposure\u2013response relationships were identified for pneumonia, herpes zoster infection, changes in platelet count, lymphopenia (Grade\u00a0\u2265\u00a04), or neutropenia (Grade\u00a0\u2265\u00a03) up to Week 26. Shallow exposure\u2013response relationships were observed for &gt;\u00a02\u00a0g\/dL decrease in hemoglobin, lymphopenia Grade\u00a0\u2265\u00a03 at Week 12\/14, and serious infections at Week 24\/26. Exposure\u2013efficacy analyses demonstrate that UPA 15\u00a0mg q.d. (once daily) dose provided the optimal benefit\u2013risk in RA through maximizing efficacy with only small incremental benefit with 30\u00a0mg q.d.; and with consistency across RA subpopulations and with UPA monotherapy or combination with conventional synthetic disease\u2010modifying antirheumatic drugs.<\/jats:p>","DOI":"10.1002\/cpt.1671","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T18:34:42Z","timestamp":1571078082000},"page":"994-1003","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Exposure\u2013Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit\u2013Risk Assessment in Rheumatoid Arthritis"],"prefix":"10.1111","volume":"107","author":[{"given":"Ahmed","family":"Nader","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed\u2010Eslam F.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Insa","family":"Winzenborg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics AbbVie Deutschland GmbH &amp; Co. 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