Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients
Negative impact of hyperglycaemia on tocilizumab therapy in Covid-19 patients
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DOI：
10.1016/j.diabet.2020.05.005
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发表时间：
2020-10-01
影响因子：
7.2
通讯作者：
Paolisso, G.
中科院分区：
文献类型：
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作者：
Marfella, R.;Paolisso, P.;Paolisso, G.
托西珠单抗通过靶向白细胞介素6受体(IL-6Rs)和减少细胞因子的释放来治疗中重度新冠肺炎肺炎。然而，尽管有这种疗法，患有糖尿病的患者与没有糖尿病的患者相比，有一个不良的病程。事实上，血糖稳态已经影响了糖尿病合并感染性疾病患者的预后。自2020年3月1日以来，在意大利感染科(博洛尼亚大学、那不勒斯万维泰利大学、圣塞巴斯蒂亚诺·卡塞塔医院)住院的475名新冠肺炎阳性患者中，31名(39.7%)高血糖患者和47名(60.3%)血糖正常患者(血糖=140 mg/dL)在入院时和住院期间进行了回顾性评估。值得注意的是，20名(%)高血糖患者和11名(23.4%)血糖正常的患者患有糖尿病(P<；0.01)。入院时，高血糖患者的IL-6水平是正常血糖患者的五倍，即使在服用曲克西平后，这种情况仍然存在(P<；0.05)。有趣的是，在风险调整的COX回归分析中，高血糖患者服用曲西他滨未能降低严重后果的风险，与正常血糖患者不同(P<；0.009)。此外，在高血糖患者中，较高的IL-6血浆水平降低了TCZ的效果，而将IL-6水平添加到COX回归模型中会导致其效果失去显著性(P<；0.07)。此外，有证据表明，在糖尿病和非糖尿病患者的高血糖期间，使用曲克西平并不能实现最佳的新冠肺炎感染管理。这些数据可能对目前正在进行的新冠肺炎患者曲克西平疗效的临床试验以及对这一患者亚群的血糖最佳控制的临床试验感兴趣。皇冠版权所有(C)2020，由爱思唯尔·马森公司出版。版权所有。
Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels >= 140 mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P < 0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P < 0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P < 0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P < 0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset. Crown Copyright (C) 2020 Published by Elsevier Masson SAS. All rights reserved.