{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:38:38Z","timestamp":1774330718270,"version":"3.50.1"},"reference-count":19,"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 UC (NCT02065622) evaluated whether a higher adalimumab induction regimen improved patients with ulcerative colitis (UC) response, but a flat dose\u2010response relationship was found in the induction study. We investigated exposure\u2010response (ER) relationships in induction and maintenance studies considering patients\u2019 baseline characteristics. Adalimumab exposures were simulated using the established population pharmacokinetic model. Multivariable logistic regressions were used to assess the efficacy endpoints (clinical remission, endoscopic remission, endoscopic improvement) at weeks 8 and 52. In the induction study, an increasing ER trend with heterogeneity between induction regimens was shown, suggesting average concentration (C<jats:sub>avg<\/jats:sub>) had a significant impact on primary efficacy endpoints within each group. However, data were not described by a single ER curve. Using inverse effective clearance as the exposure metric described trends across induction regimens with a single curve. Patients with inherently lower effective adalimumab clearance responded better. The patient response rates at week 52 showed no heterogeneity. A short\u2010term increase in adalimumab dose did not drive better responses for induction, and apparent ER relationships were better explained by patient\u2010inherent lower clearance. Conversely, during maintenance up to week 52, increasing the concentration via dose translated to better responses more robustly. The ER findings for SERENE UC were consistent with SERENE CD.<\/jats:p>","DOI":"10.1002\/cpdd.1437","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:34:51Z","timestamp":1719923691000},"page":"1033-1043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SERENE ER Analysis Part 2 SERENE\u2010UC: Exposure\u2010response Analysis of Higher Versus Standard Adalimumab Dosing Regimens for Patients with Moderately to Severely Active Ulcerative Colitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Sven","family":"Stodtmann","sequence":"first","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mong\u2010Jen","family":"Chen","sequence":"additional","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 Germany"}],"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":"Jasmina","family":"Kalabic","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH &amp; Co. KG  Ludwigshafen Germany"}],"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":"10.14309\/ajg.0000000000000152"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.221127"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0b013e318281f2b7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.02.033"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.10.032"},{"issue":"1","key":"e_1_2_9_7_1","first-page":"A221","article-title":"Exposure\u2010efficacy relationship (ER) for adalimumab during induction phase of treatment of adult patients with moderate to severe ulcerative colitis","volume":"1","author":"Mostafa NM ED","year":"2013","journal-title":"United European Gastroenterol J"},{"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 (N Y)"},{"issue":"1","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"S001","DOI":"10.1093\/ecco-jcc\/jjz203.000","article-title":"OP01 higher vs. standard adalimumab maintenance regimens in patients with moderately to severely active ulcerative colitis: results from the SERENE\u2010UC maintenance study","volume":"14","author":"Colombel JF","year":"2020","journal-title":"J Crohn's Colitis"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-023-01221-x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12838"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.22917"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2015.120"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.MIB.0000173271.18319.53"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000057"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2021.2028619"},{"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.1438"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjad140"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1437","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T01:56:10Z","timestamp":1725242170000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1437"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,2]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/cpdd.1437"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1437","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"}}]}}