Tocilizumab, sarilumab and anakinra in critically ill patients with COVID-19: a randomised, controlled, open-label, adaptive platform trial.

Whether other immune-modulator strategies are equally effective or better is unknown.

其他免疫调节策略是否同样有效或更优尚不明确。

Methods

We investigated treatment with tocilizumab, sarilumab, anakinra and no immune modulator in these patients.

我们研究了在这些患者中使用托珠单抗、萨利单抗、阿那金拉和不使用免疫调节剂的治疗效果。

In this ongoing, adaptive platform trial in 133 sites in 9 countries, we randomly assigned patients with allocation ratios dependent on the number of interventions available at each site.

在这项正在进行的、适应性的平台试验中，我们在9个国家的133个地点随机分配了患者，分配比例取决于每个地点可用的干预措施数量。

The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21 in survivors.

主要结果是一个序数量表，结合了住院期间的死亡率（赋予-1分）和到第21天存活者无器官支持的天数。

The trial used a Bayesian statistical model with predefined triggers for superiority, inferiority, efficacy, equivalence or futility.

该试验使用了贝叶斯统计模型，并预设了优势、劣势、有效性、等效性或无效性的触发条件。

Results

Of 2274 critically ill participants enrolled between 25 March 2020 and 10 April 2021, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control.

在2020年3月25日至2021年4月10日期间入组的2274名危重患者中，有972名被分配至托珠单抗组，485名至沙利木单抗组，378名至阿那金拉组，418名至对照组。

Median organ support-free days were 7 (IQR -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively.

托珠单抗、沙利木单抗、阿那金拉和对照组的中位器官支持自由天数分别为7天（四分位数间距-1, 16天）、9天（四分位数间距-1, 17天）、0天（四分位数间距-1, 15天）和0天（四分位数间距-1, 15天）。

Median adjusted ORs were 1.46 (95% credible intervals (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) and 0.99 (95% CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra relative to control, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared with control.

调整后的中位数 ORs 分别为 1.46 (95% 可信区间 (CrI) 1.13, 1.87), 1.50 (95% CrI 1.13, 2.00) 和 0.99 (95% CrI 0.74, 1.35)，对于 tocilizumab、sarilumab 和 anakinra 相对于对照组，分别得出相对于对照组的 99.8%、99.8% 和 46.6% 的优越性后验概率。

All treatments appeared safe.

所有治疗措施似乎都是安全的。

Conclusions

In critically ill patients with COVID-19, tocilizumab and sarilumab have equivalent effectiveness at reducing duration of organ support and death.

在重症COVID-19患者中，托珠单抗和萨利珠单抗在减少器官支持时间和死亡率方面具有等效的有效性。

Anakinra is not effective in this population.

阿那金拉在此类人群中无效。

trial_registration_number

NCT02735707.

NCT02735707。