{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:18Z","timestamp":1791400938770,"version":"4.3.3"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023331","name":"LEO Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)\u201013, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2\u2010year impacts of IL\u201013 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate\u2010to\u2010severe AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long\u2010term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2\u2009years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17\/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (<jats:italic>IL4R<\/jats:italic>, <jats:italic>IL31<\/jats:italic>, <jats:italic>CCL17<\/jats:italic>, and <jats:italic>CCL26<\/jats:italic>), Th1 (<jats:italic>IFNG<\/jats:italic>), and Th17\/Th22 (<jats:italic>IL22<\/jats:italic>, <jats:italic>S100A7<\/jats:italic>, <jats:italic>S100A8<\/jats:italic>, and <jats:italic>S100A9<\/jats:italic>) pathways as well as increased expression of epidermal differentiation and barrier genes (<jats:italic>CLDN1<\/jats:italic> and <jats:italic>LOR<\/jats:italic>). Tralokinumab also shifted atherosclerosis signaling pathway genes (<jats:italic>SELE<\/jats:italic>, <jats:italic>IL\u201037<\/jats:italic>, and <jats:italic>S100A8<\/jats:italic>) toward non\u2010lesional expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non\u2010lesional levels, further highlighting the key role of IL\u201013 in the pathogenesis of AD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p>NCT03131648, NCT03587805.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16108","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T15:58:00Z","timestamp":1712073480000},"page":"1560-1572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Targeting <scp>IL<\/scp>\u201013 with tralokinumab normalizes type 2 inflammation in atopic dermatitis both early and at 2\u2009years"],"prefix":"10.1111","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9363-324X","authenticated-orcid":false,"given":"Emma","family":"Guttman\u2010Yassky","sequence":"first","affiliation":[{"name":"Department of Dermatology and the Immunology Institute Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kabashima","sequence":"additional","affiliation":[{"name":"Department of Dermatology Graduate School of Medicine, Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Staumont\u2010Salle","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital of Lille, INFINITE (Institute for Translational Research) U1286 Inserm, University of Lille  Lille 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