{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T04:47:55Z","timestamp":1785905275521,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Chronic spontaneous urticaria (CSU) is a mast cell-driven disorder defined by recurrent wheals, angioedema, or both, persisting for longer than six weeks without an identifiable external trigger. Second-generation H1-antihistamines remain first-line therapy, yet a large share of patients stay symptomatic after the dose is raised up to fourfold, and for more than a decade, omalizumab was the only targeted option for those who failed antihistamines. This began to change in 2025, when the interleukin-4 receptor alpha (IL-4R\u03b1) antagonist dupilumab and the oral, covalent Bruton tyrosine kinase (BTK) inhibitor remibrutinib were approved for antihistamine-refractory CSU within months of one another, while the anti-KIT monoclonal antibody barzolvolimab, which depletes mast cells, advanced into the largest phase 3 program the disease has seen. This narrative review outlines the guideline framework that still anchors CSU care, appraises the pivotal efficacy and safety data for omalizumab, dupilumab, remibrutinib, and barzolvolimab, and considers how these mechanistically distinct agents might be positioned and sequenced. The widening choice makes individualized, mechanism-informed treatment a realistic goal, but it also sharpens unresolved questions about patient selection, optimal treatment duration in a naturally remitting disease, and the long-term safety of newer oral and mast cell-depleting approaches.<\/jats:p>","DOI":"10.3390\/diseases14080276","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T13:23:20Z","timestamp":1785504200000},"page":"276","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging and Newly Approved Therapies for Antihistamine-Refractory Chronic Spontaneous Urticaria: A Narrative Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2089-8607","authenticated-orcid":false,"given":"Raghad Saeed","family":"Asiri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Aseer Central Hospital, Aseer Health Cluster, Abha 62523, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2931-7039","authenticated-orcid":false,"given":"Khaled Abdulwahab","family":"Amer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Aseer Central Hospital, Aseer Health Cluster, Abha 62523, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leen Abdulmohsin","family":"Sarhan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Aseer Central Hospital, Aseer Health Cluster, Abha 62523, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najla Ahmad","family":"Jahash","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Aseer Central Hospital, Aseer Health Cluster, Abha 62523, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham Hamoud","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Hottat Bani Tamim General Hospital, Hotat Bani Tamim 17981, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1111\/all.15090","article-title":"The international EAACI\/GA2LEN\/EuroGuiDerm\/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria","volume":"77","author":"Zuberbier","year":"2022","journal-title":"Allergy"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1001\/jama.2024.15568","article-title":"Chronic spontaneous urticaria: A review","volume":"332","author":"Kolkhir","year":"2024","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41572-022-00389-z","article-title":"Urticaria","volume":"8","author":"Kolkhir","year":"2022","journal-title":"Nat. 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