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托珠单抗治疗 COVID-19 的疗效:当前证据综述。

Efficacy of tocilizumab in COVID-19: A review of the current evidence.

机构信息

Global Health Institute, American University of Beirut, Hamra, Beirut, Lebanon.

Division of Infectious Diseases, Department of Internal Medicine, American University of Beirut Medical Center, Hamra, Beirut, Lebanon.

出版信息

Sci Prog. 2021 Jul-Sep;104(3):368504211030372. doi: 10.1177/00368504211030372.

Abstract

As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative review that aims to review the current evidence provided by randomized clinical trials (RCT) for the use of tocilizumab in COVID-19. Electronic database searches were carried out in Medline, PubMed, Embase, Google Scholar, and ongoing clinical trial registries with the period set from January 1, 2020 to February 20, 2021. Prepublication manuscripts were found using the pre-print repository medRxiv. Keywords included "COVID-19,""coronavirus,""SARS-CoV-2,""sepsis,""pneumonia,""cytokine storm,""cytokine release syndrome,""IL-6 inhibitors," and "tocilizumab," as exact phrases, and a combination of subject headings according to databases syntax. Only trials with a clear and well-defined methodology, at least 100 patients recruited, and which have had results published either after peer review or in pre-print were included. In hospitalized patients with severe COVID-19, who are hypoxic and have a CRP ≥ 75 mg/L, the current evidence favors the use of a combination of tocilizumab and corticosteroids to reduce mortality, among other clinical benefits. There is also overwhelming evidence of the good safety profile of tocilizumab with only few cases of neutropenia reported with a decrease in infection rates. Tocilizumab is currently thought to work through the inhibition of IL-6 receptors (IL-6R), preventing downstream activation of pro-inflammatory reactions and cytokine release syndrome.

摘要

随着 2019 年冠状病毒病(COVID-19)病例不断增加,报告的死亡人数也在增加。已实施公共卫生措施,但效果不一。随着疫苗在全球范围内越来越广泛地获得和使用,治疗重症 COVID-19 患者仍然是一个问题,迄今为止,只有地塞米松被证明具有治疗效果。然而,研究白细胞介素 6 抑制剂(即托珠单抗)疗效的试验一直在进行,并取得了有希望的结果。本文是一篇叙述性综述,旨在回顾随机临床试验(RCT)提供的关于托珠单抗在 COVID-19 中的应用的现有证据。在 Medline、PubMed、Embase、Google Scholar 和正在进行的临床试验注册处进行了电子数据库检索,检索时间从 2020 年 1 月 1 日至 2021 年 2 月 20 日。使用预印本存储库 medRxiv 查找预印本手稿。关键词包括“COVID-19”、“冠状病毒”、“SARS-CoV-2”、“败血症”、“肺炎”、“细胞因子风暴”、“细胞因子释放综合征”、“白细胞介素 6 抑制剂”和“托珠单抗”,作为精确短语,并根据数据库语法使用主题词的组合。仅纳入方法明确且定义明确、至少招募 100 名患者且结果已在同行评审后或预印本中发表的试验。在患有严重 COVID-19 的住院患者中,对于那些缺氧且 C 反应蛋白(CRP)≥75mg/L 的患者,目前的证据倾向于使用托珠单抗和皮质类固醇的联合治疗,以降低死亡率和其他临床益处。托珠单抗的安全性也得到了大量证据的支持,仅报告了少数中性粒细胞减少症病例,且感染率降低。托珠单抗目前被认为通过抑制白细胞介素 6 受体(IL-6R)发挥作用,从而阻止下游炎症反应和细胞因子释放综合征的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b907/10450783/382767b64f7f/10.1177_00368504211030372-fig1.jpg

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