Department of Intensive Care Medicine, Radboud University Medical Center, 6500HB, Nijmegen, The Netherlands.
Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500HB, Nijmegen, The Netherlands.
Crit Care. 2020 Dec 10;24(1):688. doi: 10.1186/s13054-020-03364-w.
A subset of critically ill COVID-19 patients develop a hyperinflammatory state. Anakinra, a recombinant interleukin-1 receptor antagonist, is known to be effective in several hyperinflammatory diseases. We investigated the effects of anakinra on inflammatory parameters and clinical outcomes in critically ill, mechanically ventilated COVID-19 patients with clinical features of hyperinflammation.
In this prospective cohort study, 21 critically ill COVID-19 patients treated with anakinra were compared to a group of standard care. Serial data of clinical inflammatory parameters and concentrations of multiple circulating cytokines were determined and aligned on start day of anakinra in the treatment group, and median start day of anakinra in the control group. Analysis was performed for day - 10 to + 10 relative to alignment day. Clinical outcomes were analyzed during 28 days. Additionally, three sensitivity analyses were performed: (1) using propensity score-matched groups, (2) selecting patients who did not receive corticosteroids, and (3) using a subset of the control group aimed to match the criteria (fever, elevated ferritin) for starting anakinra treatment.
Baseline patient characteristics and clinical parameters on ICU admission were similar between groups. As a consequence of bias by indication, plasma levels of aspartate aminotransferase (ASAT) (p = 0.0002), ferritin (p = 0.009), and temperature (p = 0.001) were significantly higher in the anakinra group on alignment day. Following treatment, no relevant differences in kinetics of circulating cytokines were observed between both groups. Decreases of clinical parameters, including temperature (p = 0.03), white blood cell counts (p = 0.02), and plasma levels of ferritin (p = 0.003), procalcitonin (p = 0.001), creatinine (p = 0.01), and bilirubin (p = 0.007), were more pronounced in the anakinra group. No differences in duration of mechanical ventilation or ICU length of stay were observed between groups. Sensitivity analyses confirmed these results.
Anakinra is effective in reducing clinical signs of hyperinflammation in critically ill COVID-19 patients. A randomized controlled trial is warranted to draw conclusion about the effects of anakinra on clinical outcomes.
一部分危重症 COVID-19 患者会出现过度炎症反应。阿那白滞素是一种重组白细胞介素-1 受体拮抗剂，已知对多种过度炎症性疾病有效。我们研究了阿那白滞素对有过度炎症反应临床特征的危重症、机械通气的 COVID-19 患者的炎症参数和临床结局的影响。
在这项前瞻性队列研究中，我们比较了 21 例接受阿那白滞素治疗的危重症 COVID-19 患者与一组标准治疗患者。在治疗组中，我们在开始使用阿那白滞素的当天，以及在对照组中中位数开始使用阿那白滞素的当天，对连续的临床炎症参数和多种循环细胞因子的浓度进行了测定和排列。分析在对齐日的-10 天到+10 天进行。在 28 天内分析临床结局。此外，还进行了三次敏感性分析：（1）使用倾向评分匹配组；（2）选择未接受皮质类固醇治疗的患者；（3）使用对照组的一个子集，旨在匹配开始阿那白滞素治疗的标准（发热、铁蛋白升高）。
两组患者的基线特征和入住 ICU 时的临床参数相似。由于指示性偏倚，阿那白滞素组在对齐日的血浆天门冬氨酸氨基转移酶（ASAT）（p=0.0002）、铁蛋白（p=0.009）和体温（p=0.001）水平显著更高。在治疗后，两组之间循环细胞因子动力学无明显差异。临床参数的下降，包括体温（p=0.03）、白细胞计数（p=0.02）、铁蛋白（p=0.003）、降钙素原（p=0.001）、肌酐（p=0.01）和胆红素（p=0.007）水平，在阿那白滞素组更为明显。两组之间机械通气时间或 ICU 住院时间无差异。敏感性分析证实了这些结果。
阿那白滞素可有效减轻危重症 COVID-19 患者的过度炎症表现。需要进行随机对照试验来得出关于阿那白滞素对临床结局影响的结论。
