ABSTRACT

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex immunological upper airway disease . CRSwNP, particularly in Caucasians, often has a more distinct T2 inflammatory endotype. IL-4 and IL-13 are key upstream cytokines that help establish and sustain T2 inflammation as well as strongly influencing tissue remodeling. They have a shared signaling receptor IL-4Rα. An attractive and novel therapeutic approach is by way of blocking IL-4 and IL-13 simultaneously via inhibiting IL-4Rα. Dupilumab is a murine derived fully human monoclonal inhibitory antibody directed against IL-4Rα which thereby prevents IL-4/IL-13 cell signaling. Following successful Phase 3 studies dupilumab has become the first licensed biologic for treating CRSwNP.

Areas covered: This review covers the essential immunology of CRSwNP in the context of IL-4 and IL-13 signaling via IL-4Rα. The potential mechanisms by which therapeutic improvements occur with dupilumab are evaluated. IL-4, IL-13, dupilumab and rhinosinusitis were used as the search terms in PubMed and Google Scholar through to August 2020.

Expert commentary: Dupilumab has the potential to transform the care for patients with CRSwNP. It is essential that further studies are conducted promptly to identify disease-specific biomarkers and clinical traits to guide clinicians on best patient selection thereby ensuring optimal dupilumab outcomes.

摘要

简介：慢性鼻窦炎伴鼻息肉 (CRSwNP) 是一种复杂的免疫学上呼吸道疾病。CRSwNP，特别是在白种人中，通常具有更明显的 T2 炎症内型。IL-4 和 IL-13 是关键的上游细胞因子，有助于建立和维持 T2 炎症以及强烈影响组织重塑。它们有一个共享的信号受体 IL-4Rα。一种有吸引力且新颖的治疗方法是通过抑制 IL-4Rα 同时阻断 IL-4 和 IL-13。Dupilumab 是一种鼠源性全人源单克隆抑制性抗体，针对 IL-4Rα，从而阻止 IL-4/IL-13 细胞信号传导。在成功的 3 期研究之后，dupilumab 已成为第一个获得许可的治疗 CRSwNP 的生物制剂。

涵盖的领域：本综述涵盖了在 IL-4 和 IL-13 信号通过 IL-4Rα 的背景下 CRSwNP 的基本免疫学。评估了 dupilumab 治疗改善的潜在机制。直到 2020 年 8 月，IL-4、IL-13、dupilumab 和鼻窦炎被用作 PubMed 和 Google Scholar 中的搜索词。

专家评论：Dupilumab 有可能改变 CRSwNP 患者的护理。必须迅速进行进一步研究以确定疾病特异性生物标志物和临床特征，以指导临床医生选择最佳患者，从而确保最佳的 dupilumab 结果。