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托珠单抗在入住重症监护病房的重症 COVID-19 患者中的疗效以及非托珠单抗 COVID-19 特异性医学治疗方法的作用。

Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics.

作者信息

Elhazmi Alyaa, Rabie Ahmed A, Al-Omari Awad, Mufti Hani N, Sallam Hend, Alshahrani Mohammed S, Mady Ahmed, Alghamdi Adnan, Altalaq Ali, Azzam Mohamed H, Sindi Anees, Kharaba Ayman, Al-Aseri Zohair A, Almekhlafi Ghaleb A, Tashkandi Wail, Alajmi Saud A, Faqihi Fahad, Alharthy Abdulrahman, Al-Tawfiq Jaffar A, Melibari Rami Ghazi, Arabi Yaseen M

机构信息

Department of Critical Care, Dr. Sulaiman Al-Habib Medical Group, Riyadh 11643, Saudi Arabia.

Critical Care Department, King Saud Medical City, Riyadh 11196, Saudi Arabia.

出版信息

J Clin Med. 2023 Mar 16;12(6):2301. doi: 10.3390/jcm12062301.

Abstract

BACKGROUND

Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published.

OBJECTIVES

We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs.

METHODS

A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge.

RESULTS

A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) ( = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) ( = 0.799) remained as a predictor for an increase in 28 day survival.

CONCLUSION

The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

摘要

背景

托珠单抗是一种单克隆抗体,被提议用于治疗与重症新型冠状病毒肺炎(COVID-19)相关的细胞因子释放综合征(CRS)。先前发表的报告表明,托珠单抗可能改善入住重症监护病房(ICU)的重症患者的临床结局。然而,关于同时用于COVID-19的其他药物治疗对这一结局的作用,尚未有确切数据公布。

目的

我们旨在比较入住ICU的接受托珠单抗治疗的重症COVID-19患者与未接受托珠单抗治疗的匹配患者的总体结局,同时控制其他混杂因素,包括入住ICU的重症患者的药物治疗。

方法

2020年3月1日至2020年10月31日期间,在沙特阿拉伯14家医院的ICU对重症COVID-19患者进行了一项前瞻性、观察性、多中心队列研究。采用倾向评分匹配法比较接受托珠单抗治疗的患者与未接受托珠单抗治疗的患者。此外,采用对数秩检验比较接受托珠单抗治疗的患者与未接受托珠单抗治疗的患者的28天住院生存率。然后,对匹配组进行多因素逻辑回归分析,以评估通过匹配28天住院生存率无法排除的其余同时使用的药物治疗的影响。主要结局指标为患者总体28天住院生存率,次要结局为ICU住院时间和ICU存活至出院。

结果

共纳入1470例未匹配患者,其中426例接受了托珠单抗治疗。倾向评分匹配患者总数为1278例。总体而言,28天住院生存率在未匹配的非托珠单抗组(586例;56.1%)和托珠单抗组(269例;63.1%)之间存在显著差异(P值 = 0.016),在倾向评分匹配分析中,非托珠单抗组(466.7例;54.6%)和托珠单抗组(269例;63.1%)之间的差异更大(P值 = 0.005)。匹配模型成功匹配了两组用于治疗COVID-19的常见药物治疗。两种药物治疗仍存在显著差异,托珠单抗组更具优势。对倾向评分匹配患者的28天住院生存率进行了多因素逻辑回归分析。结果显示,无论是类固醇(比值比:1.07(95%置信区间:0.75 - 1.53))(P = 0.697)还是法匹拉韦(比值比:1.08(95%置信区间:0.61 - 1.9))(P = 0.799)都不再是28天生存率增加的预测因素。

结论

入住ICU的重症COVID-19患者接受托珠单抗治疗可提高总体28天住院生存率,这可能不受同时使用的其他COVID-19药物治疗的影响,尽管需要进一步研究来证实这一点。

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