{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:43:51Z","timestamp":1793371431213,"version":"4.5.0"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atopic dermatitis is a chronic inflammatory skin disorder driven largely by type 2 immune pathways, with interleukin-13 (IL-13) playing a central role in disease pathogenesis. Biologics targeting IL-13, including tralokinumab and lebrikizumab, have demonstrated efficacy in clinical trials; however, the therapeutic value of intra-class switching following primary treatment failure remains poorly defined, and existing real-world reports rarely distinguish primary from secondary failure. This gap is particularly relevant for patients with limited systemic treatment options, in whom treatment sequencing decisions carry greater clinical weight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>We report a 29-year-old man with lifelong moderate atopic dermatitis and limited systemic treatment options due to contraindications and prior treatment inefficacy. He demonstrated confirmed primary failure to tralokinumab, with persistent disease activity, despite good adherence. Prior to switching to lebrikizumab, EASI was 9, POEM 16, and DLQI 8, with the patient achieving marked improvement in disease severity within four months (EASI 0, POEM 5, DLQI 7), alongside early improvement in pruritus. At six months, disease control remained substantially improved (EASI 1.4), with good tolerability and no requirement for rescue systemic therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Despite targeting the same cytokine, tralokinumab and lebrikizumab exhibit distinct receptor-binding properties, with lebrikizumab preserving IL-13 interaction with the IL-13Ra2 decoy receptor, potentially enhancing cytokine clearance and modulating downstream signalling. This case demonstrates a clinically meaningful improvement in disease severity following primary failure to tralokinumab, supporting the concept of functional heterogeneity within IL-13 inhibition and suggesting that primary failure does not imply class-wide inefficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case provides evidence that primary failure to tralokinumab may not preclude response to lebrikizumab, possibly supporting intra-class heterogeneity among IL-13 inhibitors. Sequential IL-13 inhibition may represent a rational therapeutic option in patients with limited treatment options. Further studies are needed to identify predictors of response and optimise biologic sequencing in atopic dermatitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1953586","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:19:41Z","timestamp":1790144381000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Report: Differential response to IL-13 inhibition: lebrikizumab following primary tralokinumab failure in atopic dermatitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Shukry","family":"Abdi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Cifrea","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Chelsea and Westminster Hospital NHS Foundation Trust","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","author":"Silverberg","year":""},{"key":"B2","doi-asserted-by":"publisher","first-page":"S65","DOI":"10.1016\/j.jaci.2017.01.011","article-title":"The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies","volume":"139","author":"Brunner","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1177\/1203475420982553","article-title":"Inhibition of IL-13: a new pathway for atopic dermatitis","volume":"25","author":"Ratnarajah","year":"2020","journal-title":"J Cutan Med Surg"},{"key":"B4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/all.13954","article-title":"Interleukin-13: targeting an underestimated cytokine in atopic dermatitis","volume":"75","author":"Bieber","year":"2019","journal-title":"Allergy"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.20660","article-title":"Real-world experience of switching from tralokinumab to lebrikizumab in atopic dermatitis","volume":"39","author":"Hagino","year":"2025","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1016\/j.jaad.2021.01.012","article-title":"Facial and neck erythema associated with dupilumab treatment: a systematic review","volume":"84","author":"Jo","year":"2021","journal-title":"J Am Acad Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2839","DOI":"10.1038\/s41467-024-46540-0","article-title":"Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells","volume":"15","author":"Bangert","year":"2024","journal-title":"Nat Commun"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.7573\/dic.2021-1-7","article-title":"Selective IL-13 inhibitors for the treatment of atopic dermatitis","volume":"10","author":"Gon\u00e7alves","year":"2021","journal-title":"Drugs Context"},{"key":"B9","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jaci.2019.06.016","article-title":"Clinical review: pruritus in allergy and immunology","volume":"144","author":"Yang","year":"2019","journal-title":"J Allergy Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.cell.2017.08.006","article-title":"Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch","volume":"171","author":"Oetjen","year":"2017","journal-title":"Cell"},{"key":"B11","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1016\/j.jaci.2022.01.028","article-title":"Mechanistic insights into the antipruritic effects of lebrikizumab, an anti\u2013IL-13 mAb","volume":"150","author":"Miron","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jaci.2025.02.029","article-title":"Endotypes of atopic dermatitis","volume":"156","author":"Fyhrquist","year":"","journal-title":"J Allergy Clini Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1001\/jamadermatol.2020.0079","article-title":"Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis","volume":"156","author":"Guttman-Yassky","year":"2020","journal-title":"JAMA Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/j.jaad.2018.01.017","article-title":"Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: a randomized, placebo-controlled phase II trial (TREBLE)","volume":"78","author":"Simpson","year":"2018","journal-title":"J Am Acad Dermatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1056\/NEJMoa2206714","article-title":"Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis","volume":"388","author":"Silverberg","year":"2023","journal-title":"N Eng J Med"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1953586\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:19:42Z","timestamp":1790144382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1953586\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":15,"alternative-id":["10.3389\/fmed.2026.1953586"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1953586","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"article-number":"1953586"}}