{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:07:22Z","timestamp":1773032842649,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    To characterize the relationship between cendakimab exposure and the longitudinal efficacy endpoint dysphagia days (DD), E\u2013R analyses were performed using data from the EE\u2010001 study (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009427) with eosinophilic esophagitis. DD\u2014a bounded, discrete endpoint assessed over 14\u2010day period via modified daily symptom diary (mDSD)\u2014was modeled using a latent variable indirect response (IDR) model coupled with a combined uniform\u2010binomial (CUB) distribution. The latent variable, representing the underlying disease status, was dynamically modulated by placebo and drug effects (a function of individual\u2010predicted exposure) to govern the binomial probability of DD, while the uniform component captured the residual variability in patient\u2010reported outcomes. Inter\u2010individual variability was estimated for baseline DD, maximum placebo effect, and maximum drug effect. Covariates, including steroid inadequate response or intolerance (Steroid IR\/I) status and baseline DD, were incorporated in the final model based on the clinical relevance. The estimated placebo half\u2010life was ~28\u2009weeks, estimated EC\n                    <jats:sub>50<\/jats:sub>\n                    was 76.5\u2009\u03bcg\/mL, corresponding to an EC\n                    <jats:sub>90<\/jats:sub>\n                    of ~688\u2009\u03bcg\/mL, indicating steepness of the\n                    <jats:italic>E<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    curve. Model\u2010based simulations showed that both 360\u2009mg QW and QW\u2010to\u2010Q2W regimens reduced DD compared to placebo at Week 48, with mean reductions of ~1.65 and ~1.36\u2009days, respectively. Covariate\u2010stratified simulations suggested consistent responses across sex, age, and race. Steroid IR\/I and baseline DD influenced treatment response magnitude but did not warrant dose modification. These findings support QW\u2010to\u2010Q2W as an effective maintenance posology and the utility of latent variable IDR models with appropriate likelihoods for modeling bounded, discrete longitudinal endpoints in E\u2013R analyses.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70199","type":"journal-article","created":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:38:42Z","timestamp":1769222322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Latent Variable Indirect Response Modeling of Cendakimab Exposure\u2013Response for Longitudinal Dysphagia Days Using a Combined Uniform\u2010Binomial Likelihood Framework"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4430-7165","authenticated-orcid":false,"given":"Shengnan","family":"Du","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3302-8742","authenticated-orcid":false,"given":"Jessica","family":"Wojciechowski","sequence":"additional","affiliation":[{"name":"PumasAI Inc  Dover Delaware USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peijin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urvi","family":"Aras","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bindu","family":"Murthy","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-0276","authenticated-orcid":false,"given":"Jun","family":"Shen","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5642-2960","authenticated-orcid":false,"given":"Anna","family":"Kondic","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7812-2778","authenticated-orcid":false,"given":"Chuanpu","family":"Hu","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2014.02.006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-017-0525-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2009.03383.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.90"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000471"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.10.051"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.03.036"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2024.107708"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3768\/rtipress.2015.bk.0014.1509"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-020-00478-5"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7525-4-79"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2022.106717"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1200\/EDBK_175418"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.0830"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-020-00212-x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41687-023-00651-2"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100241"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"}],"container-title":["CPT: Pharmacometrics &amp; 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