Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19
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DOI：
10.1093/cid/ciaa954
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发表时间：
2021-07-15
影响因子：
11.8
通讯作者：
Pogue, Jason M.
中科院分区：
文献类型：
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作者：
Somers, Emily C.;Eschenauer, Gregory A.;Pogue, Jason M.
背景资料。重症冠状病毒病2019(新冠肺炎)可表现为快速失代偿和呼吸衰竭，并伴有炎症标志物升高，这与IL-6阻断是批准的治疗方法的细胞因子释放综合征一致。我们在单中心需要机械通气的新冠肺炎患者队列中评估了托西珠单抗阻断IL-6的有效性和安全性。主要终点是插管后的存活概率；二次分析包括结合重叠感染的有序疾病严重程度量表。采用多变量COX回归结合倾向分数倒置治疗概率加权(IPTW)对接受tocilizumab治疗的患者和未接受tocilizumab治疗的患者的预后进行评估。154名患者纳入研究，其中78人接受tocilizumab治疗，76人未接受治疗。中位随访期为47天(28-67天)。两组之间的基线特征相似，尽管接受tocilizumab治疗的患者更年轻(平均：55岁比60岁)，较不可能患有慢性肺部疾病(10%比28%)，并且插管时D-二聚体水平较低(中位数：2.4vs6.5 mg/dL)。在IPTW调整的模型中，tocilizumab与死亡风险降低45%(HR，0.55；95%CI，0.33-0.90)和改善序贯结果量表上的状况[OR每增加1级，0.58；.36-0.94]相关。虽然tocilizumab与重叠感染患者的比例增加有关(54%比26%；P<；.001)，但在接受tocilizumab治疗的患者和没有重叠感染的患者中，28天的病死率没有差异(22%比15%；P=.42)。金黄色葡萄球菌占细菌性肺炎的50%。在这组使用机械通气的新冠肺炎患者中，尽管重叠感染的发生率较高，但托西珠单抗仍与较低的死亡率有关。
Background. Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment.Methods. We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW).Results. 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for similar to 50% of bacterial pneumonia.Conclusions. In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.