Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
PLoS One. 2023 Dec 29;18(12):e0295838. doi: 10.1371/journal.pone.0295838. eCollection 2023.
Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration.
The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery.
Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly.
Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020-00174824).
阿那白滞素和托珠单抗用于治疗严重的 COVID-19，但此前仅有一项随机对照试验（RCT）同时研究了这两种药物。我们进行了一项多中心 RCT，比较了阿那白滞素或托珠单抗与常规治疗（UC）用于高危病情恶化的成年人。
该研究于 2020 年 6 月至 2021 年 3 月进行。入选标准需要≥5 升/分钟的氧气以维持外周血氧饱和度≥93%，C 反应蛋白（CRP）>70mg/L，铁蛋白>500μg/L，至少有两个点得 1 分，其中 1 分是淋巴细胞<1x109/L；D-二聚体≥0.5mg/L 和乳酸脱氢酶（LDH）≥8 微卡/升。患者以 1:1:1 的比例随机接受单次托珠单抗（8mg/kg）或阿那白滞素 100mg IV QID 治疗 7 天或单独 UC。主要结局是恢复时间。
当托珠单抗成为常规治疗的一部分时，提前终止了入组。在计划入组的 195 名患者中，77 名患者被随机分配至 UC 组、27 名患者接受阿那白滞素治疗、28 名患者接受托珠单抗治疗。恢复时间的中位数分别为 15、15 和 11 天。UC 组与阿那白滞素组的恢复率比值为 0.91，0.47 至 1.78，95%[CI]，p=0.8；UC 组与托珠单抗组的恢复率比值为 1.13，0.55 至 2.30；p=0.7。托珠单抗（以及在一定程度上阿那白滞素）在一些次要结局上较 UC 有非显著的优势趋势。安全性特征无显著差异。
试验的过早关闭使得无法得出明确的结论。与常规治疗相比，阿那白滞素或托珠单抗并未显著缩短临床恢复时间。（IMMCoVA，NCT04412291，EudraCT：2020-00174824）。
