{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:09:21Z","timestamp":1790082561329,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic spontaneous urticaria (CSU) remains inadequately controlled by H1\u2010antihistamines and omalizumab in a substantial minority of patients at every age. Recognition that mast cell activation proceeds through IgE\u2010independent as well as IgE\u2010dependent routes has exposed several tractable targets\u2014Bruton's tyrosine kinase, the IL\u20104\/IL\u201013 axis, KIT, MRGPRX2 and the JAK\u2013STAT pathway\u2014hence the resulting expansion of the treatment armamentarium is the largest since omalizumab. The oral BTK inhibitor remibrutinib is now licensed for adults in the United States and European Union; Dupilumab, approved from 12\u2009years of age in 2025, was extended to children aged 2\u201311\u2009years in 2026 on basis of extrapolated efficacy supported by paediatric pharmacokinetic and safety data. Barzolvolimab has completed Phase 3 enrolment of 1939 adults, briquilimab, EVO756, EP262 and rilzabrutinib are advancing in adults and ligelizumab failed to demonstrate superiority over omalizumab. This review appraises these agents by mechanism, efficacy, safety and probable place in therapy and argues that the limiting factor is no longer the number of druggable targets but the distribution and quality of the evidence. Adults dominate the trial populations; adolescents are enrolled as underpowered subgroups; dedicated paediatric evidence is essentially confined to dupilumab; and older adults\u2014in whom comorbidity, polypharmacy and the cardiovascular and malignancy signals of JAK inhibition matter most\u2014are almost never analyzed separately. Head\u2010to\u2010head and sequencing trials, endotype\u2010stratified patient selection, age\u2010inclusive trial design and long\u2010term safety data are the immediate priorities if mechanism\u2010based treatment is to reach patients at every stage of life.<\/jats:p>","DOI":"10.1111\/cea.70437","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:18:52Z","timestamp":1790079532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Omalizumab: Emerging Biologic and Small Molecule Therapies in Chronic Spontaneous Urticaria"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9028-0635","authenticated-orcid":false,"given":"Sahibpreet","family":"Kaur","sequence":"first","affiliation":[{"name":"Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-101X","authenticated-orcid":false,"given":"Muthu Sendhil","family":"Kumaran","sequence":"additional","affiliation":[{"name":"Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saumya","family":"Singh","sequence":"additional","affiliation":[{"name":"Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0348-0815","authenticated-orcid":false,"given":"Davinder","family":"Parsad","sequence":"additional","affiliation":[{"name":"Postgraduate Institute of Medical Education and Research (PGIMER)  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"issue":"1","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1038\/s41572-022-00389-z","article-title":"Urticaria","volume":"8","author":"Kolkhir P.","year":"2022","journal-title":"Nature Reviews Disease Primers"},{"issue":"6","key":"e_1_2_10_3_1","first-page":"1866","article-title":"Urticaria and Angioedema Across the Ages","volume":"8","author":"Saini S.","year":"2020","journal-title":"Journal of Allergy and Clinical Immunology: In Practice"},{"issue":"15","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.2147\/JAA.S379912","article-title":"Prevalence, Clinical Manifestations, Treatment, and Clinical Course of Chronic Urticaria in Elderly: A Systematic Review","volume":"20","author":"Kulthanan K.","year":"2022","journal-title":"Journal of Asthma and Allergy"},{"issue":"6","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","DOI":"10.1111\/pai.70132","article-title":"Omalizumab in Pediatric Chronic Spontaneous Urticaria: A Systematic Review and Meta\u2010Analysis of Efficacy and Safety","volume":"36","author":"Alomari O.","year":"2025","journal-title":"Pediatric Allergy and Immunology"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/all.70210"},{"issue":"5","key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.3345\/kjp.2015.58.5.159","article-title":"Approaches to the Diagnosis and Management of Chronic Urticaria in Children","volume":"58","author":"Choi S. 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