Tocilizumab Has Limited Clinical Utility for COVID19 in Two Multiethnic Community Hospitals

K. Cervellione, G. Dadi, N. Hameedi, M. Pignanelli, B. Kuriakose, V. Zafonte, T. Ullah, J. Robitsek, G. Pena Fatule, H. Patel, D. Wisa, K. Gafoor, M. Walczyszyn, J. Shakil, F. Bagheri, A. Solinas, R. Mendelson
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Abstract

The COVID19 pandemic has pushed healthcare workers to utilize available therapeutics, often with limited evidence. Theoretically, IL6 inhibitors could help to stop or reverse the damage caused by COVID19 cytokine storm. Published evidence from the United States is conflicting and is largely from academic institutions and nonminority populations. This study assessed the clinical utility of open-label tocilizumab in two multiethnic community hospitals in Queens, NY.Tocilizumab (8mg/kg) was given to 114 patients for treatment of COVID19- related respiratory failure between April 4 and May 19 2020 (96% received 1 dose). A retrospective cohort study was performed to determine 28-day clinical success, defined as achieving a score of 1 using a 6-point scale (1=no O2 requirement or discharged home on 2L/min;2=low-flow O2 in hospital ≤6L/min;3=O2 >6 to ≤15L/min;4=high-flow, CPAP, or BiPAP;5=mechanically ventilated (MV);6=expired). The decision to administer tocilizumab was made by a committee based on unstable or worsening respiratory status. Mean patient age was 60 years (SD=11);77(67%) were male. 25% were Asian, 23% black (31% black Hispanic), 36% white (73% white Hispanic), and 14% other. A majority of patients had at least 1 significant comorbidity, including HTN 56%, DM 40%, HLD 43%, and COPD/asthma 16%. Median days of symptoms at dose was 14(IQR 10-19);SpO2 on RA at admission was 82%(IQR 67-88%). Baseline status by ordinal scale was as follows: 2= 9(8%);3=33(29%);4=38(33%);5=34(30%) (IQR 1-2 days on vent). Median CRP=19.9, d-dimer=1658, ferritin=593, and LDH=1561. 28-day success was achieved in 35(31%) patients;62(55%) patients expired or were MV on day 28. Of patients who were on high-flow, CPAP, BiPAP or MV at baseline, 80% expired or were on MV on day 28. Estimated mortality in all hospitalized patients during the time frame at these hospitals was 36%. No significant differences were seen in labs, comorbidities or age between patients who did and did not have clinical success. Higher baseline ordinal scale score was predictive of mortality.Tocilizumab provided little to no clinical utility, especially in those with high oxygenation needs at time of dosing (success rate <20%). The main limitation is lack of a control group;however mortality was strikingly high. This in part may be due to the demographic and clinical characteristics of our sample.
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托珠单抗在两家多民族社区医院对covid - 19的临床效用有限
covid - 19大流行迫使卫生保健工作者利用现有的治疗方法,但往往证据有限。理论上,il - 6抑制剂可以帮助阻止或逆转covid - 19细胞因子风暴造成的损害。来自美国的公开证据相互矛盾,而且主要来自学术机构和非少数族裔人群。本研究评估了开放标签tocilizumab在纽约皇后区两家多民族社区医院的临床应用。2020年4月4日至5月19日期间,114例患者接受Tocilizumab (8mg/kg)治疗covid - 19相关呼吸衰竭(96%接受1剂)。通过一项回顾性队列研究来确定28天的临床成功,定义为使用6分制达到1分(1=无氧气需求或出院时为2L/min;2=医院低流量O2≤6L/min;3=O2 >6至≤15L/min;4=高流量、CPAP或BiPAP;5=机械通气(MV);6=过期)。给予tocilizumab的决定是由一个基于不稳定或恶化呼吸状态的委员会做出的。患者平均年龄60岁(SD=11),男性77例(67%)。25%为亚洲人,23%为黑人(31%为西班牙裔黑人),36%为白人(73%为西班牙裔白人),14%为其他人种。大多数患者至少有1种显著合并症,包括HTN 56%, DM 40%, HLD 43%, COPD/哮喘16%。给药后出现症状的中位天数为14天(IQR 10-19);入院时RA的SpO2为82%(IQR 67-88%)。按顺序量表计算基线状态:2= 9(8%),3=33(29%),4=38(33%),5=34(30%)(IQR 1-2天)。中位CRP=19.9, d-二聚体=1658,铁蛋白=593,LDH=1561。35例(31%)患者28天成功;62例(55%)患者在28天死亡或MV。在基线时使用高流量、CPAP、BiPAP或MV的患者中,80%的患者在第28天死亡或使用MV。在这些医院的时间框架内,所有住院患者的估计死亡率为36%。在实验室、合并症或年龄方面,有临床成功和没有临床成功的患者没有显著差异。较高的基线顺序量表评分可预测死亡率。Tocilizumab几乎没有提供临床效用,特别是在给药时需要高氧的患者(成功率<20%)。主要的限制是缺乏一个对照组,然而死亡率是惊人的高。这部分可能是由于我们样本的人口统计学和临床特征。
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