Department of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, Japan.
Department of Dermatology, Graduate School of Medical Science Kyoto Prefectural University of Medicine, Kyoto, Japan.
Allergol Int. 2020 Apr;69(2):187-196. doi: 10.1016/j.alit.2020.01.002. Epub 2020 Jan 30.
Interleukin (IL)-4 and IL-13, signature type 2 cytokines, exert their actions by binding to two types of receptors sharing the IL-4R α chain (IL-4Rα). Since IL-4 and IL-13 play important and redundant roles in the pathogenesis of allergic diseases, blocking both the IL-4 and IL-13 signals would be a powerful and effective strategy for treating allergic diseases. Dupilumab (Dupixent®) is a fully human monoclonal antibody recognizing IL-4Rα and blocking both the IL-4 and IL-13 signals. Dupilumab was first prescribed for atopic dermatitis (AD) patients and has been widely approved for adult patients with moderate to severe AD since 2018. Dupilumab has since been used for asthma, receiving approval for uncontrolled asthma in 2019. A phase 3 study using dupilumab for chronic rhinosinusitis with nasal polyps (CRSwNP) has been just completed, with positive results. Several clinical trials of dupilumab for other diseases in which type 2 inflammation is dominant are now underway. It is hoped that dupilumab will open the door to a new era for treating allergic patients with AD, asthma, and CRSwNP, and for more patients with type 2 inflammations.
白细胞介素 (IL)-4 和 IL-13 是 2 型细胞因子的标志性分子,通过与共享 IL-4Rα 链 (IL-4Rα) 的两种受体结合来发挥作用。由于 IL-4 和 IL-13 在过敏疾病的发病机制中发挥着重要且冗余的作用,因此阻断 IL-4 和 IL-13 信号将是治疗过敏疾病的一种强大而有效的策略。度普利尤单抗 (Dupixent®) 是一种识别 IL-4Rα 并阻断 IL-4 和 IL-13 信号的全人源单克隆抗体。度普利尤单抗最初被用于特应性皮炎 (AD) 患者,自 2018 年以来已广泛批准用于中重度 AD 的成年患者。此后,度普利尤单抗已用于治疗哮喘,并于 2019 年获得了对未控制哮喘的批准。一项使用度普利尤单抗治疗慢性鼻-鼻窦炎伴鼻息肉 (CRSwNP) 的 3 期研究刚刚完成,结果为阳性。目前正在进行几项针对其他以 2 型炎症为主的疾病的度普利尤单抗临床试验。人们希望度普利尤单抗将为治疗 AD、哮喘和 CRSwNP 的过敏患者以及更多 2 型炎症患者开辟一个新时代。