Therapeutic Approaches for Chronic Spontaneous Urticaria: Current and Emerging Options

Chronic spontaneous urticaria (CSU) is a recurrent, mast cell-mediated skin condition characterized by wheals, angioedema, or both lasting over six weeks without a known cause. Its underlying mechanisms are still being researched but involve some immune dysregulation, including Immunoglobulin E (IgE) mediated mast cell activation and autoimmune signaling. This leads to unpredictable flare-ups that significantly affect a patient’s quality of life. Current treatment guidelines recommend a stepwise approach. Second-generation H1-antihistamines are the first-line therapy, though many patients experience incomplete relief even after increasing the dosage. Omalizumab, an anti-IgE monoclonal antibody, is the standard second-line treatment and has transformed management for patients who do not respond to antihistamines by providing significant symptom control and improving quality of life. Dupilumab, which targets the Interleukin-4 (IL-4) and Interleukin-13 (IL-13) pathways, and Tezepelumab, which blocks thymic stromal lymphopoietin (TSLP), have shown substantial efficacy in recent trials, expanding biologics available for more severe cases of CSU. Emerging therapies continue to advance the field by targeting different points in mast cell activation. Remibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, and Barzolvolimab, an anti-KIT proto-oncogene, receptor tyrosine kinase (KIT) monoclonal antibody, has demonstrated promising results in reducing symptoms and improving disease control. Together, these treatments mark a shift towards precision medicine in CSU, focusing on targeted, mechanism-based therapies that not only improve symptom relief but also aim for long-term remission and reduced disease burden. This review focuses on approved and emerging biologic therapies for CSU from the past to present, with significant developments from 2014 to 2025.