{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:56:21Z","timestamp":1792716981318,"version":"4.5.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"\n Importance<\/jats:title>\n Chronic spontaneous urticaria (CSU) is an inflammatory disease characterized by recurrent pruritic hives and\/or angioedema. Many patients with CSU remain symptomatic despite standard-of-care, histamine 1\u2013receptor antagonist (H1-AH) treatment. Dupilumab blocks IL-4\/IL-13 signaling and is approved in multiple disease states associated with type 2 inflammation. In the phase 3 LIBERTY-CSU CUPID-A trial, dupilumab significantly reduced itch and hives severity in anti\u2212immunoglobulin E (IgE)\u2212naive patients with CSU uncontrolled with H1-AH. However, a replicate trial (CUPID-C) was required per US Food and Drug Administration registration requirements.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To further evaluate the efficacy and safety of dupilumab vs placebo in anti-IgE\u2013naive patients with CSU uncontrolled by H1-AH.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n The LIBERTY-CSU CUPID-C (2022-2024) was a randomized, placebo-controlled, double-blind, 24-week phase 3 trial using the same trial design as CUPID-A (2019-2021). CUPID-A and CUPID-C were performed in 10 countries in Asia, Europe, and North and South America with anti-IgE\u2212naive patients aged 6 to 80 years with CSU uncontrolled with H1-AH. Data were analyzed from August to September 2024.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Dupilumab or placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n In CUPID-C and pooled CUPID-A and -C analyses, change from baseline at week 24 in Itch Severity Score over 7 days (ISS7) or Urticaria Activity Score over 7 days (UAS7), with the other as a key secondary end point, per regional regulatory requirements.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The CUPID-C analysis included 151 participants (mean [SD] age, 44.7 [16.9] years; 106 females [70.2%]), of whom 77 (51%) were taking H1-AH at a dosage higher than recommended, and 90 (59.6%) had a baseline UAS7\u2009of 28 or greater. Significant improvements in ISS7 and UAS7 were observed with dupilumab vs placebo at week 24. Least squares mean (SE) changes were \u22128.64 (1.41) vs \u22126.10 (1.40), respectively (difference: \u22122.54 points [95% CI, \u22124.65 to \u22120.43];\n P<\/jats:italic>\n \u2009=\u2009.02) for ISS7 and \u221215.86 (2.66) vs \u221211.21 (2.65), respectively (difference: \u22124.65 points [95% CI, \u22128.65 to \u22120.65];\n P<\/jats:italic>\n \u2009=\u2009.02) for UAS7. CUPID-A and -C combined data (289 participants) demonstrated greater improvements in UAS7 and ISS7. Safety outcomes were generally consistent with the known dupilumab safety profile; 77 patients (53.5%) taking dupilumab vs 81 patients (55.9%) taking placebo reported treatment-emergent adverse events in the pooled analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The CUPID-C randomized clinical trial confirmed CUPID-A findings, and pooled data demonstrated dupilumab significantly reduced urticaria activity by reducing itch and hives severity in anti-IgE\u2013naive patients with CSU who remained symptomatic despite the use of H1-AH.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04180488<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamadermatol.2025.6023","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T16:30:35Z","timestamp":1771432235000},"page":"350","source":"Crossref","is-referenced-by-count":8,"title":["Dupilumab in Patients With Chronic Spontaneous Urticaria"],"prefix":"10.1001","volume":"162","author":[{"given":"Thomas B.","family":"Casale","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Department of Medicine, University of South Florida, Tampa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarbjit S.","family":"Saini","sequence":"additional","affiliation":[{"name":"Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Ben-Shoshan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Allergy, Clinical Immunology and Dermatology, McGill University Health Centre, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Gim\u00e9nez-Arnau","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Hospital del Mar Research Institute, Universitat Pompeu Fabra, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Internal Medicine, University of Cincinnati College of Medicine and Bernstein Clinical Research Center, Cincinnati, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koremasa","family":"Hayama","sequence":"additional","affiliation":[{"name":"Division of Cutaneous Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Amin","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lacey B.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Bauer","sequence":"additional","affiliation":[{"name":"Sanofi, Morristown, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Dakin","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Laws","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Radin","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Makhija","sequence":"additional","affiliation":[{"name":"Sanofi, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"3","key":"doi250074r1","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1111\/j.1398-9995.2010.02496.x","article-title":"Unmet clinical needs in chronic spontaneous urticaria. 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