Department of Dermatology and Allergy, Dermatological Allergology, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Division of Allergy and Immunology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Tex.
J Allergy Clin Immunol Pract. 2021 Mar;9(3):1067-1078. doi: 10.1016/j.jaip.2020.11.043.
Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease. The rationale for this is supported by the key role of IgE and its high-affinity receptor, FcεRI, in the degranulation of skin mast cells that drives the development of the signs and symptoms of CSU, itchy wheals, and angioedema. Here, we review the current understanding of the pathogenesis of CSU and its autoimmune endotypes. We describe the mechanisms of action of omalizumab, the only biologic currently approved for CSU, its efficacy and ways to improve it, biomarkers for treatment response, and strategies for its discontinuation. We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss targets for novel biologics and where we stand with their clinical development. These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future.
慢性自发性荨麻疹（CSU）治疗指南建议在抗组胺药难治性疾病患者中使用 IgE 靶向生物制剂奥马珠单抗。IgE 及其高亲和力受体 FcεRI 在驱动 CSU 体征和症状（瘙痒性风团和血管性水肿）发展的皮肤肥大细胞脱颗粒中的关键作用为这一建议提供了依据。在这里，我们回顾了 CSU 及其自身免疫表型的发病机制的现有认识。我们描述了奥马珠单抗的作用机制，奥马珠单抗是目前唯一获批用于 CSU 的生物制剂，其疗效及其提高方法、治疗反应的生物标志物以及停药策略。我们提供了有关在 CSU 中使用其他疾病治疗药物（包括度普利尤单抗、贝那利珠单抗、美泊利珠单抗、瑞利珠单抗和司库奇尤单抗）的标签外用途的信息。最后，我们讨论了新型生物制剂的靶标以及它们在临床开发中的地位。这些靶标包括 IgE/ligelizumab、IgE/GI-310、胸腺基质淋巴细胞生成素/tezepelumab、C5a 受体/avdoralimab、唾液酸结合免疫球蛋白样凝集素 8/lirentelimab、CD200R/LY3454738 和 KIT/CDX-0159。我们的目的是提供有关生物制剂在 CSU 患者治疗中的使用的最新信息和指导，无论是现在还是在不久的将来。
