与基于体重给药相比，在新冠肺炎危重症患者中降低托珠单抗固定剂量至400mg静脉注射：一项前后队列研究。
Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study.
作者信息
Stukas Sophie, Goshua George, Kinkade Angus, Grey Rebecca, Mah Gregory, Biggs Catherine M, Jamal Shahin, Thiara Sonny, Lau Tim T Y, Piszczek Jolanta, Partovi Nilu, Sweet David D, Lee Agnes Y Y, Wellington Cheryl L, Sekhon Mypinder S, Chen Luke Y C
机构信息
Djavad Mowafaghian Centre for Brain Health, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Section of Hematology, Yale University School of Medicine, New Haven, CT, USA.
出版信息
Lancet Reg Health Am. 2022 Jul;11:100228. doi: 10.1016/j.lana.2022.100228. Epub 2022 Mar 23.
BACKGROUND
Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab.
METHODS
This was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness.
FINDINGS
152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (=2) vs 8% (=5) vs 13% (=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations.
INTERPRETATION
Both doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option.
FUNDING
This work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.
背景
白细胞介素-6抑制剂可降低重症新型冠状病毒肺炎（COVID-19）的死亡率。不列颠哥伦比亚省于2021年1月开始对重症COVID-19患者使用托珠单抗8mg/kg（最大剂量800mg），但由于药物短缺，于2021年4月将剂量降至400mg静脉固定剂量。本研究的目的有两个：比较这两种策略的生理反应和临床结局，并研究对所有患者使用400mg治疗与对一半患者使用8mg/kg而另一半患者不使用托珠单抗治疗的成本效益。
方法
这是一项对接受托珠单抗治疗的重症COVID-19患者进行的单中心前后队列研究，以及一个仅接受地塞米松治疗的对照队列研究。比较接受两种剂量托珠单抗的患者与仅接受地塞米松治疗的患者的生理反应和临床结局。我们构建了一个决策树模型来研究成本效益。
结果
共纳入152例患者；40例接受托珠单抗8mg/kg，59例接受400mg，53例仅接受地塞米松治疗。在托珠单抗8mg/kg组、400mg组和仅接受地塞米松治疗组中，C反应蛋白（CRP）中位数分别从103mg/L降至5.2mg/L、从96mg/L降至6.8mg/L和从81.3mg/L降至48mg/L。28天死亡率分别为5%（=2）、8%（=5）和13%（=7），所有两两比较均无显著差异。在假设每生命年支付意愿阈值为50000加元的情况下，在10000次蒙特卡洛模拟中，51.6%的情况下对所有患者使用400mg而非对一半患者使用8mg/kg具有成本效益。
解读
两种剂量的托珠单抗在降低炎症方面表现相当，28天死亡率相似。在不考虑公平性的情况下，对所有患者提供400mg托珠单抗的净货币效益与对一半患者提供8mg/kg相当。在持续存在药物短缺的情况下，固定剂量400mg的托珠单抗可能是一种实用、可行且经济的选择。
资助
这项工作得到了许氏与泰勒家族对温哥华总医院基金会的捐赠以及耶鲁大学伯纳德·G·福格奖学金的支持。
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