影响 COVID-19 诱导的细胞因子释放综合征中托珠单抗治疗结局的主要因素有哪些?
What are the main factors affecting the outcome of tocilizumab therapy in COVID-19-induced cytokine release syndrome?
机构信息
Department of Rheumatology, Demiroglu Bilim University School of Medicine, Istanbul, Turkey.
Department of Radiology, Demiroglu Bilim University School of Medicine,Istanbul, Turkey.
出版信息
Eur J Rheumatol. 2022 Jul;9(3):126-131. doi: 10.5152/eurjrheum.2022.21010.
OBJECTIVE
Recommendations for the treatment of cytokine release syndrome/macrophage activation syndrome (MAS) associated with coronavirus disease-2019 (COVID-19) are still of poor quality. IL-6 is an important therapeutic target as a main mediator of cytokine storm. The aim of our study was to evaluate the tocilizumab (TCZ) efficacy and factors affecting the therapy outcome.
METHODS
This retrospective study included 27 patients treated with TCZ for COVID-19-MAS. All patients in this study were treated with TCZ (intravenously, at a dose of 8 mg kg1 ) in addition to standard therapy. Clinical improvement (survival and decreased oxygen demand) on the 10-14th days and secondary infection rate were assessed.
RESULTS
In our 27 treated patients, 14 (51.8%) received TCZ in the intensive care unit (ICU) and seven (25.9%) were need to invasive mechanical ventilation (IMV). Fifteen (55.6%) of these patients revealed a good clinical response (four patients discharge from the ICU and 11 patients who followed-up in nonICU beds showed a decrease in oxygen demand). TCZ was significantly less effective in patients having high Murray lung injury score, low PO2/FiO2 ratio, IMV, and ICU admission (P < .05). Severity of hypoxemia was found as a single independent risk factor in the multivariable analysis (P < .05). Secondary bacterial infections rate was significantly higher in intubated patients (P < .01) or treated in the ICU (P ¼ .01).
CONCLUSION
TCZ was showed limited efficacy for COVID-19-related MAS. The most important predictive indicator for therapy outcome was found as the severity of hypoxemia. In addition, IMV and/or ICU was associated with the poor outcome and high side effect. So, controlled trials are still needed to confirm the indications and timing of TCZ therapy.
目的
与 2019 年冠状病毒病(COVID-19)相关的细胞因子释放综合征/巨噬细胞活化综合征(MAS)的治疗建议质量仍然较差。白细胞介素 6(IL-6)是细胞因子风暴的主要介质,是重要的治疗靶点。本研究旨在评估托珠单抗(TCZ)的疗效及其影响治疗效果的因素。
方法
这是一项回顾性研究,共纳入 27 例接受 TCZ 治疗的 COVID-19-MAS 患者。所有患者在标准治疗的基础上均接受 TCZ(静脉注射,剂量为 8 mg·kg-1)治疗。评估第 10-14 天的临床改善(存活和减少氧气需求)和继发性感染率。
结果
在接受治疗的 27 例患者中,14 例(51.8%)在重症监护病房(ICU)接受 TCZ 治疗,7 例(25.9%)需要有创机械通气(IMV)。其中 15 例(55.6%)患者的临床反应良好(4 例患者从 ICU 出院,11 例患者在非 ICU 病床的氧气需求减少)。TCZ 在肺部损伤评分高、PO2/FiO2 比值低、IMV 和 ICU 入院的患者中的疗效明显较差(P<0.05)。多变量分析发现,低氧血症的严重程度是唯一的独立危险因素(P<0.05)。在接受气管插管的患者(P<0.01)或在 ICU 接受治疗的患者(P=0.01)中,继发性细菌感染的发生率显著更高。
结论
TCZ 对 COVID-19 相关 MAS 的疗效有限。治疗效果的最重要预测指标是低氧血症的严重程度。此外,IMV 和/或 ICU 与不良预后和高副作用相关。因此,仍需要进行对照试验来确认 TCZ 治疗的适应证和时机。