Bulkhi Adeeb A
Internal Medicine Department, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Clin Drug Investig. 2025 Sep 17. doi: 10.1007/s40261-025-01480-5.
Chronic urticaria (CU) is a complex, disabling skin disease characterized by recurrent, pruritic wheals and frequently angioedema lasting for 6 weeks or more. Although non-sedating H1-antihistamines remain the first-line therapy, a significant subset of patients (50%) remains symptomatic despite antihistamines, underscoring an unmet need for more targeted treatments. Recent advances in our understanding of CU pathophysiology have led to the development of biologic agents-most notably omalizumab and dupilumab-as well as an expanding pipeline of small-molecule therapies targeting key intracellular signaling pathways (e.g., Bruton's tyrosine kinase [BTK] and Janus kinase [JAK] inhibitors). Therapeutic targets for biologics in chronic spontaneous urticaria (CSU) include IgE, IL-4/IL-13, and IL-5 pathways. This review provides a comprehensive overview of the underlying immunopathogenesis of CSU in adults, critically examines the limitations of conventional therapy (primarily second-generation H1-antihistamines), and reviews the current status and future prospects of biologic and small-molecule treatments. It synthesizes the rapidly evolving landscape of these therapies focusing on therapeutic mechanisms of biologic and small-molecule therapies, recent clinical trial data, and potential for personalized treatment, building on and extending prior reviews. We also discuss practical considerations-including endotyping, cost-effectiveness, and long-term safety, and outline future research directions toward personalized management of chronic urticaria.
慢性荨麻疹（CU）是一种复杂的、使人衰弱的皮肤病，其特征为反复出现的瘙痒性风团，常伴有血管性水肿，持续6周或更长时间。尽管非镇静性H1抗组胺药仍是一线治疗药物，但仍有相当一部分患者（50%）在使用抗组胺药后仍有症状，这突出表明对更具针对性治疗的需求尚未得到满足。我们对CU病理生理学认识的最新进展导致了生物制剂的开发——最显著的是奥马珠单抗和度普利尤单抗——以及针对关键细胞内信号通路的小分子疗法（如布鲁顿酪氨酸激酶[BTK]和Janus激酶[JAK]抑制剂）的不断增加。慢性自发性荨麻疹（CSU）生物制剂的治疗靶点包括IgE、IL-4/IL-13和IL-5通路。本综述全面概述了成人CSU的潜在免疫发病机制，批判性地审视了传统疗法（主要是第二代H1抗组胺药）的局限性，并回顾了生物制剂和小分子治疗的现状与未来前景。它综合了这些疗法快速发展的情况，重点关注生物制剂和小分子疗法的治疗机制、近期临床试验数据以及个性化治疗的潜力，在之前综述的基础上进行拓展。我们还讨论了实际考虑因素——包括内型分型、成本效益和长期安全性，并概述了慢性荨麻疹个性化管理的未来研究方向。
