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白细胞介素-17在斑块状银屑病中的作用:司库奇尤单抗的治疗潜力

Role of IL-17 in plaque psoriasis: therapeutic potential of ixekizumab.

作者信息

Hanley Tessa L, Yiu Zenas Zn

机构信息

Fairfield General Hospital, Bury.

Centre for Dermatology; Centre for Pharmacoepidemiology and Drug Safety, Manchester Academic Health Science Centre, Manchester, UK.

出版信息

Ther Clin Risk Manag. 2017 Mar 13;13:315-323. doi: 10.2147/TCRM.S111107. eCollection 2017.

Abstract

Developments in the understanding of the immunopathogenesis of psoriasis have identified interleukin (IL)-17 as the key proinflammatory cytokine in the pathogenesis of plaque psoriasis, with the consequent development of drugs that target this cytokine or associated receptors. Ixekizumab is a subcutaneously administered humanized monoclonal antibody, which acts to neutralize IL-17A. This article reviews the role of IL-17 in the pathogenesis of psoriasis, the biological and pharmacokinetics of ixekizumab and the safety profile and the clinical efficacy of ixekizumab in Phase III clinical trials. Phase III clinical trials of ixekizumab have so far demonstrated excellent early clinical efficacy, with a comparable safety profile to the existing biologic therapies for psoriasis. To further assess its position in the treatment algorithm for psoriasis, a further head to head RCT with secukinumab could be established, alongside comparative effectiveness studies from observational research. In addition, trials are needed to assess its role in those with tumor necrosis factor inhibitors/ustekinumab resistant disease. However, it is clear that the IL-17 antagonists have changed the benchmark for clinical efficacy, and it is likely that ixekizumab along with the other IL-17 antagonists are set to achieve a new standard of care in the treatment of moderate to severe plaque psoriasis.

摘要

对银屑病免疫发病机制认识的进展已确定白细胞介素(IL)-17是斑块状银屑病发病机制中的关键促炎细胞因子,随之开发出了靶向该细胞因子或相关受体的药物。司库奇尤单抗是一种皮下注射的人源化单克隆抗体,其作用是中和IL-17A。本文综述了IL-17在银屑病发病机制中的作用、司库奇尤单抗的生物学特性和药代动力学、安全性概况以及其在III期临床试验中的临床疗效。司库奇尤单抗的III期临床试验迄今已证明其具有出色的早期临床疗效,安全性与现有的银屑病生物疗法相当。为了进一步评估其在银屑病治疗方案中的地位,可以开展一项与苏金单抗的进一步头对头随机对照试验,同时进行观察性研究的比较有效性研究。此外,还需要进行试验来评估其在对肿瘤坏死因子抑制剂/优特克单抗耐药的患者中的作用。然而,很明显,IL-17拮抗剂已经改变了临床疗效的基准,司库奇尤单抗以及其他IL-17拮抗剂很可能会在中重度斑块状银屑病的治疗中达到新的护理标准。

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