Pelaia Corrado, Vatrella Alessandro, Gallelli Luca, Terracciano Rosa, Navalesi Paolo, Maselli Rosario, Pelaia Girolamo
a Department of Medical and Surgical Sciences , University "Magna Græcia" of Catanzaro , Catanzaro , Italy.
b Department of Medicine , Surgery and Dentistry, University of Salerno , Salerno , Italy.
Expert Opin Biol Ther. 2017 Dec;17(12):1565-1572. doi: 10.1080/14712598.2017.1387245. Epub 2017 Oct 8.
Dupilumab is a fully human IgG4 monoclonal antibody directed against the α subunit of the interleukin (IL)-4 receptor (IL-4Rα). Since the activation of IL-4Rα is utilized by both IL-4 and IL-13 to mediate their pathophysiological effects, dupilumab behaves as a dual antagonist of these two sister cytokines, which blocks IL-4/IL-13-dependent signal transduction. Areas covered: Herein, the authors review the cellular and molecular pathways activated by IL-4 and IL-13, which are relevant to asthma pathobiology. They also review: the mechanism of action of dupilumab, the phase I, II and III studies evaluating the pharmacokinetics as well as the safety, tolerability and clinical efficacy of dupilumab in asthma therapy. Expert opinion: Supported by a strategic mechanism of action, as well as by convincing preliminary clinical results, dupilumab currently appears to be a very promising biological drug for the treatment of severe uncontrolled asthma. It also may have benefits to comorbidities of asthma including atopic dermatitis, chronic sinusitis and nasal polyposis.
度普利尤单抗是一种全人源IgG4单克隆抗体,靶向白细胞介素(IL)-4受体(IL-4Rα)的α亚基。由于IL-4和IL-13均利用IL-4Rα的激活来介导其病理生理效应,度普利尤单抗可作为这两种姐妹细胞因子的双重拮抗剂,阻断IL-4/IL-13依赖的信号转导。涵盖领域:本文中,作者回顾了与哮喘病理生物学相关的、由IL-4和IL-13激活的细胞和分子途径。他们还回顾了:度普利尤单抗的作用机制、评估度普利尤单抗在哮喘治疗中的药代动力学以及安全性、耐受性和临床疗效的I期、II期和III期研究。专家观点:在具有战略意义的作用机制以及令人信服的初步临床结果的支持下,度普利尤单抗目前似乎是一种非常有前景的生物药物,用于治疗严重的难治性哮喘。它对哮喘的合并症可能也有益处,包括特应性皮炎、慢性鼻窦炎和鼻息肉病。