{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:04:45Z","timestamp":1777399485897,"version":"3.51.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"NIHR Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ciclosporin A (CsA) is approved for severe atopic dermatitis (AD), but its efficacy may not be optimal, and its toxicity limits longer-term use. The recently approved lebrikizumab has demonstrated robust efficacy and favourable safety in adults and adolescents with moderate-to-severe AD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the efficacy and safety of lebrikizumab combined with topical corticosteroids (TCS) in adults and adolescents with moderate-to-severe AD who had a history of inadequate response to CsA or for whom CsA was not medically advisable.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This was a placebo-controlled, randomized phase IIIb clinical study (ADvantage; NCT05149313). Patients were randomized 2 : 1 to receive either lebrikizumab 250\u2005mg plus TCS (with a loading dose of lebrikizumab 500\u2005mg at baseline and week 2) or placebo plus TCS, delivered subcutaneously, every 2 weeks (Q2W), for the 16-week induction period. Following this, all patients received lebrikizumab 250\u2005mg Q2W during a 36-week open-label maintenance period (with TCS use at investigator discretion). The primary endpoint was the proportion of patients who achieved \u2265 75% improvement from baseline in Eczema Area and Severity Index (EASI 75) at week 16.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In total, 331 patients were randomized, 220 to receive lebrikizumab plus TCS and 111 to receive placebo plus TCS. At week 16, a significantly higher proportion of the lebrikizumab group vs. the placebo group achieved EASI 75 (68.4% vs. 40.8%; P &amp;lt; 0.001). At week 16, a greater proportion of the treatment group achieved \u2265 90% improvement from baseline in EASI (EASI 90) (42.9% vs. 20.8%; P &amp;lt; 0.001), Investigator\u2019s Global Assessment of clear\/almost clear skin (IGA 0\/1) with \u2265 2-point improvement from baseline (42.0% vs. 24.5%; P &amp;lt; 0.01), and \u2265 4-point improvement in pruritus numeric rating scale (NRS) (49.9% vs. 29.7%; P &amp;lt; 0.05). At week 52, the proportion of patients treated with lebrikizumab with\/without TCS who achieved EASI 75 and EASI 90 further increased to 88.9% and 71.7%, respectively; 64.4% achieved IGA 0\/1 response and 71.3% achieved a \u2265 4-point improvement in pruritus NRS. The incidence of treatment-emergent adverse events (TEAEs) was 62.3% in the lebrikizumab plus TCS group vs. 53.2% in the placebo plus TCS group at week 16, and 76.9% in the lebrikizumab group at week 52. Serious adverse events and TEAEs leading to discontinuation at week 16 were low and similar in lebrikizumab vs. placebo groups (1.4% vs. 0.9% and 0.5% vs. 0.9%, respectively), and remained low at week 52 (5.9% and 2.5%, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Lebrikizumab 250\u2005mg Q2W combined with TCS significantly improved signs and symptoms of AD at week 16 in adults and adolescents with moderate-to-severe AD and history of inadequate response to CsA or for whom CsA was not medically advisable, and those benefits were maintained and\/or further improved by week 52. Safety was consistent with the known lebrikizumab safety profile.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljaf285","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T10:31:15Z","timestamp":1758623475000},"page":"876-888","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and safety of lebrikizumab in adult and adolescent patients with moderate-to-severe atopic dermatitis inadequately controlled with or ineligible for ciclosporin A: a placebo-controlled, randomized phase IIIb clinical study (ADvantage)"],"prefix":"10.1093","volume":"193","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-6481","authenticated-orcid":false,"given":"Richard B","family":"Warren","sequence":"first","affiliation":[{"name":"Dermatology Centre, Northern Care Alliance NHS Foundation Trust and Division of Musculoskeletal and Dermatological Sciences, Manchester NIHR Biomedical Research Centre, Manchester Academic Health Science Centre, 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C","family":"Szepietowski","sequence":"additional","affiliation":[{"name":"Division of Dermatology, Venereology and Clinical Immunology, Faculty of Medicine, Wroclaw University of Science and Technology , Wroclaw ,","place":["Poland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H Chih-ho","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Skin Science, University of British Columbia , Vancouver, BC ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanislav","family":"Mihaylov","sequence":"additional","affiliation":[{"name":"Almirall SA , Barcelona ,","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meritxell","family":"Falqu\u00e9s","sequence":"additional","affiliation":[{"name":"Almirall SA , Barcelona 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