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靶向严重哮喘中的白细胞介素-4 和白细胞介素-13 通路:现有知识和未来需求。

Targeting the interleukin-4 and interleukin-13 pathways in severe asthma: current knowledge and future needs.

机构信息

Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, Texas, USA.

Department of Respiratory Medicine and Allergology, Skäne University Hospital, Lund, Sweden.

出版信息

Curr Opin Pulm Med. 2018 Jan;24(1):50-55. doi: 10.1097/MCP.0000000000000436.

Abstract

PURPOSE OF REVIEW

Severe asthma is a heterogeneous disease that can be classified into phenotypes and endotypes based upon clinical or biological characteristics. Interleukin (IL)-4 and IL-13 play a key role in type 2 (T2) asthma. This article reviews the signaling pathway of IL-4 and IL-13 and highlights its targeted therapy in severe asthma.

RECENT FINDINGS

Several clinical trials of biologics targeting the IL-4/IL-13 pathway have recently been completed. In patients with severe, uncontrolled asthma, targeting IL-13 alone with biologics including lebrikizumab and tralokinumab has not shown consistent reduction in asthma exacerbations. Simultaneous targeting of both IL-4 and IL-13 by blocking IL-4 receptor α using dupilumab has yielded more consistent results in reducing asthma exacerbations and improving lung function, especially in patients with increased blood eosinophils. Other biomarkers of T2 inflammation such as exhaled nitric oxide and serum periostin may also predict response to biologics targeting the IL-4/IL-13 pathway.

SUMMARY

No biologic targeting the IL-4/IL-13 pathway is currently available for treatment of asthma, but emerging data suggest that biologics targeting IL-4 and IL-13 together may benefit patients with T2 high asthma. Additional data are needed about long-term efficacy and safety prior to incorporating these drugs into routine clinical practice.

摘要

综述目的

重度哮喘是一种异质性疾病,可以根据临床或生物学特征分为表型和内型。白细胞介素(IL)-4 和 IL-13 在 2 型(T2)哮喘中起关键作用。本文综述了 IL-4 和 IL-13 的信号通路,并强调了其在重度哮喘中的靶向治疗。

最新发现

最近已经完成了几项针对 IL-4/IL-13 通路的生物制剂的临床试验。在重度、未控制的哮喘患者中,单独针对 IL-13 的生物制剂,如 lebrikizumab 和 tralokinumab,并未显示出一致的哮喘恶化减少。使用 dupilumab 同时阻断 IL-4 和 IL-13 受体α靶向治疗,在减少哮喘恶化和改善肺功能方面产生了更一致的结果,尤其是在血嗜酸性粒细胞增多的患者中。T2 炎症的其他生物标志物,如呼气一氧化氮和血清骨膜蛋白,也可能预测对 IL-4/IL-13 通路靶向生物制剂的反应。

总结

目前尚无针对 IL-4/IL-13 通路的生物制剂可用于治疗哮喘,但新出现的数据表明,同时靶向 IL-4 和 IL-13 的生物制剂可能有益于 T2 高哮喘患者。在将这些药物纳入常规临床实践之前,还需要更多关于长期疗效和安全性的数据。

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