{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:38:02Z","timestamp":1774330682398,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>SERENE CD (NCT02065570) evaluated whether a higher adalimumab induction dose would improve patients with Crohn disease response and suggested a flat dose\u2010response relationship for efficacy in the induction study. We investigated exposure\u2010response relationships in induction and maintenance studies considering patients\u2019 baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Efficacy end points (clinical remission\/endoscopic response) at Weeks 4, 12, and 56 were evaluated in exposure\u2010response analyses using multivariable logistic regression. Analyses showed an increasing trend with heterogeneity between induction regimens, which suggested that average concentration has an impact on coprimary efficacy end points within each group, but data did not fit a single\u2010response curve. Although higher concentrations within arms were associated with improved outcomes, increasing the concentration through a higher induction dose was not associated with increasing clinical remission\/endoscopic response at Week 4\/12. A model including inverse effective clearance eliminated heterogeneity and described trends across induction regimens with a single curve. In the maintenance study, the response rates at Week 56 showed no heterogeneity. In the induction study, patients with lower effective adalimumab clearance responded better, whereas in the maintenance study average concentration drove primary efficacy end points at Week 56. Research extending these findings to other indications is needed.<\/jats:p>","DOI":"10.1002\/cpdd.1438","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:07:01Z","timestamp":1719922021000},"page":"1024-1032","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SERENE ER Analysis Part 1\u2010SERENE CD: Exposure\u2010Response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients With Moderately to Severely Active Crohn Disease"],"prefix":"10.1002","volume":"13","author":[{"given":"Mong\u2010Jen","family":"Chen","sequence":"first","affiliation":[{"name":"AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Victoria","family":"Ponce\u2010Bobadilla","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Hessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Stodtmann","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Hessen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra P.","family":"Song","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tricia K.","family":"Finney\u2010Hayward","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nael M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"AbbVie  North Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03671.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2018.27"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.01.044"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.041"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.03.050"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2005.11.030"},{"issue":"3","key":"e_1_2_9_8_1","first-page":"139","article-title":"Clinical implications of the recent dose\u2010ranging studies of adalimumab","volume":"16","author":"Feagan B","year":"2020","journal-title":"Gastroenterol Hepatol (NY)"},{"issue":"4","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s40262-023-01221-x","article-title":"Assessing the impact of immunogenicity and improving prediction of trough concentrations\u2010population pharmacokinetic modeling of adalimumab in patients with Crohn's disease and ulcerative colitis","volume":"62","author":"Ponce\u2010Bobadilla AV","year":"2023","journal-title":"Clin Pharmacokient"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12838"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.22917"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.120"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.25122\/jml-2021-0311"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000057"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2021.2028619"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjad140"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy129"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1429"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1437"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T01:55:57Z","timestamp":1725242157000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,2]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/cpdd.1438"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1438","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,2]]},"assertion":[{"value":"2024-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-29","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}