{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:32:58Z","timestamp":1784957578369,"version":"3.55.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"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":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Amlitelimab is a fully human, nondepleting, anti\u2010OX40 ligand monoclonal antibody being investigated for the treatment of moderate\u2010to\u2010severe atopic dermatitis (AD) in adults and adolescents. Population pharmacokinetic (PopPK) and pharmacokinetic\/pharmacodynamic\u2010Eczema Area and Severity Index (PopPK\/PD\u2010EASI) models were used to inform dosing regimen selection for amlitelimab phase 3 trials. The PopPK model was developed using phase 1 (healthy volunteers) and phase 2 (participants with AD) trial data, including individual exposure variables from the STREAM\u2010AD phase 2b trial following subcutaneous amlitelimab doses ranging from 62.5 to 250\u2009mg given every 4\u2009weeks (Q4W). The PopPK model was used to compute exposures for an extended dosing regimen of 250\u2009mg Q12W (with 500\u2009mg loading dose [+LD]). The PopPK\/PD\u2010EASI model was developed from phase 2 trials to predict treatment responses (EASI values) with selected dosing scenarios. Finally, the dose for individuals with lower body weight (i.e., &lt;\u200940\u2009kg) was determined. Utilizing the PopPK model, the amlitelimab 250\u2009mg Q12W\u2009+\u2009LD computed exposures were between the exposures of 62.5\u2009mg Q4W and 250\u2009mg Q4W\u2009+\u2009LD efficacious doses in the STREAM\u2010AD trial. Using the PopPK\/PD\u2010EASI model, the simulated efficacy for dosing scenarios of 250\u2009mg Q12W\u2009+\u2009LD regimen from initiation or 250\u2009mg Q4W\u2009+\u2009LD for 24\u2009weeks followed by Q12W to Week 60 was similar to continuous 250\u2009mg Q4W. Simulations identified that a twofold dose reduction would allow participants &lt;\u200940\u2009kg to achieve amlitelimab exposures within the range observed in participants \u2265\u200940\u2009kg on 250\u2009mg Q4W or Q12W. These results support evaluation of a Q12W dosing regimen for adults and adolescents in phase 3 trials.<\/jats:p>","DOI":"10.1002\/psp4.70121","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T06:20:21Z","timestamp":1759386021000},"page":"2161-2172","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population Pharmacokinetic and Pharmacodynamic Modeling for the Prediction of the Extended Amlitelimab Phase 3 Dosing Regimen in Atopic Dermatitis"],"prefix":"10.1002","volume":"14","author":[{"given":"Gilles","family":"Tiraboschi","sequence":"first","affiliation":[{"name":"Sanofi  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9557-3642","authenticated-orcid":false,"given":"Kim","family":"Papp","sequence":"additional","affiliation":[{"name":"Alliance Clinical Trials and Probity Medical Research  Waterloo Ontario Canada"},{"name":"Division of Dermatology Temerty School of Medicine, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-3817","authenticated-orcid":false,"given":"Thomas","family":"Bieber","sequence":"additional","affiliation":[{"name":"Christine K\u00fchne\u2212Center for Allergy Research and Education, Medicine Campus  Davos Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3944-252X","authenticated-orcid":false,"given":"Stephan","family":"Weidinger","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-667X","authenticated-orcid":false,"given":"Lisa","family":"Beck","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Rochester Medical Center  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9804-3874","authenticated-orcid":false,"given":"Chih\u2010Hung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology Kaohsiung Chang Gung Memorial Hospital  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9968-1517","authenticated-orcid":false,"given":"John T.","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Formerly Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2337-2045","authenticated-orcid":false,"given":"Karl","family":"Yen","sequence":"additional","affiliation":[{"name":"Sanofi  Rotkreuz Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4563-8927","authenticated-orcid":false,"given":"Charlotte","family":"Bernigaud","sequence":"additional","affiliation":[{"name":"Sanofi  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fabre","sequence":"additional","affiliation":[{"name":"Sanofi  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Hurbin","sequence":"additional","affiliation":[{"name":"Sanofi  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(20)31286\u20101"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2021.05.075"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.19391"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1610020"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.19574"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010023\u201000992\u20104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjd\/ljad240"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13070587"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2539"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.10.031"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/der.0000000000000895"},{"key":"e_1_2_10_13_1","volume-title":"NONMEM 7.5 Users Guides. 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