The new revolution in the treatment of chronic urticaria, present and future of an effective and safe approach.

Abstract

Chronic spontaneous urticaria (CSU) is a heterogeneous mast cell-driven disease associated with a substantial burden on patients' quality of life. Although most patients achieve disease control with guideline-recommended therapies, a relevant proportion remains refractory, highlighting important unmet needs. This narrative review summarizes current, emerging, and investigational treatments for CSU, discussing them with a pathogenesis-driven and endotype-oriented approach. Established therapies, including second-generation H1-antihistamines and omalizumab, are discussed alongside recently approved and upcoming agents such as dupilumab and Bruton's tyrosine kinase inhibitors, particularly remibrutinib. In addition, novel strategies targeting mast cell survival and activation (antireceptor tyrosine kinase therapies), intracellular signaling pathways (Janus Kinase and Tyrosine kinase 2inhibitors), immunoglobulin E-independent activation (Mas-related G protein-coupled receptor X2 antagonists), and next-generation anti-immunoglobulin E antibodies are reviewed. Beyond symptom control, the concepts of complete disease control, remission, relapse, and disease modification are examined. The evolving therapeutic landscape of CSU is expected to enable a more personalized management, with the potential to achieve sustained remission and, ultimately, disease modification in selected patients.