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一种管理 COVID-19 的新方法。IL-6 拮抗剂:西妥昔单抗。

A New Approach to the Management of COVID-19. Antagonists of IL-6: Siltuximab.

机构信息

Pharmacology Unit, Biomedical Sciences Department, University of Alcalá, Madrid, 28805, Alcalá de Henares, Spain.

出版信息

Adv Ther. 2022 Mar;39(3):1126-1148. doi: 10.1007/s12325-022-02042-3. Epub 2022 Jan 24.

Abstract

Since the beginning of the pandemic, numerous national and international clinical trials have been conducted with a large number of drugs. Many of them are intended for the treatment of other pathologies; however, despite the great effort made, no specific drug is available for the treatment of the symptoms of respiratory disease caused by SARS-CoV-2 infection. The aim of this article is to provide data to justify the use of drugs to tackle the effects produced by IL-6 as the main inflammatory mediator in patients with COVID-19 with severe respiratory complications, considering all clinical evidence linking the poor prognosis of these patients with increased IL-6 levels in the context of cytokine release syndrome. Furthermore, data are provided to justify the proposal of a rational dosing of siltuximab, a monoclonal antibody specifically targeting IL-6, based on RCP levels, considering the limited results published so far on the use of this drug in COVID-19. A literature search was conducted on the clinical trials of siltuximab published to date as well as on the different IL-6 signalling pathways and the effects of its overexpression. Knowledge of the mechanisms of action on these pathways may provide important information for the design of drugs useful in the treatment of these patients. This article describes the characteristics, properties, mechanism of action, therapeutic uses and clinical studies conducted with siltuximab so far. The results confirm that administration of siltuximab downregulates IL-6 levels, thereby reducing the inflammatory process in COVID-19 patients with severe respiratory disease, suggesting that it can be successfully used to prevent cytokine release syndrome and death from this cause.

摘要

自疫情开始以来,已经进行了许多国家和国际临床试验,涉及大量药物。其中许多药物旨在治疗其他疾病;然而,尽管付出了巨大的努力,仍然没有针对 SARS-CoV-2 感染引起的呼吸道疾病症状的特效药物。本文的目的是提供数据,证明使用药物来解决 COVID-19 患者中由 IL-6 引起的炎症反应的有效性,因为 IL-6 是导致严重呼吸并发症的主要炎症介质,考虑到所有将这些患者的不良预后与细胞因子释放综合征中 IL-6 水平升高联系起来的临床证据。此外,还提供了数据,证明根据 RCP 水平合理调整西妥昔单抗(一种专门针对 IL-6 的单克隆抗体)剂量的合理性,因为迄今为止关于这种药物在 COVID-19 中的使用的有限结果表明,考虑到迄今为止已发表的关于该药物在 COVID-19 中的使用的有限结果,基于 RCP 水平合理调整西妥昔单抗剂量是合理的。对迄今为止发表的关于西妥昔单抗的临床试验以及不同的 IL-6 信号通路及其过表达的影响进行了文献检索。对这些途径的作用机制的了解可能为设计治疗这些患者的有用药物提供重要信息。本文描述了西妥昔单抗的特性、性质、作用机制、治疗用途和迄今为止进行的临床研究。结果证实,西妥昔单抗的给药可降低 IL-6 水平,从而减轻 COVID-19 严重呼吸疾病患者的炎症反应,表明它可成功用于预防细胞因子释放综合征和由此引起的死亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/622c/8918133/a8094389a255/12325_2022_2042_Fig1_HTML.jpg

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