Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts.
JAMA Intern Med. 2021 Jan 1;181(1):41-51. doi: 10.1001/jamainternmed.2020.6252.
Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness.
To test whether tocilizumab decreases mortality in this population.
DESIGN, SETTING, AND PARTICIPANTS: The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding.
Treatment with tocilizumab in the first 2 days of ICU admission.
Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences.
Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%).
Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.
重要性：目前需要能够改善 2019 年冠状病毒病（COVID-19）危重症患者生存率的疗法。托珠单抗是一种针对白细胞介素 6 受体的单克隆抗体，可能会对抗重症 COVID-19 患者的细胞因子释放综合征。
目的：检验托珠单抗是否能降低此类患者的死亡率。
设计、地点和参与者：本研究的数据来自 2020 年 3 月 4 日至 5 月 10 日期间美国 68 家医院参与的一项多中心队列研究，该研究纳入了 4485 名 COVID-19 成年重症患者。将入住 ICU 的 COVID-19 危重症患者按其在 ICU 入院后前两天是否接受托珠单抗治疗进行分类。数据是通过回顾性收集的，直到 2020 年 6 月 12 日。采用逆概率加权 Cox 回归模型进行混杂因素调整。
暴露因素：ICU 入院后前两天接受托珠单抗治疗。
主要结局和测量指标：通过风险比（HR）比较死亡时间，通过风险差异比较 30 天死亡率。
结果：在纳入分析的 3924 名患者中（2464 名男性[62.8%]；中位年龄 62 岁[四分位距 {IQR}，52-71]），433 名（11.0%）患者在 ICU 入院后前两天接受了托珠单抗治疗。接受托珠单抗治疗的患者更年轻（中位年龄 58 岁[IQR，48-65]岁 vs 63 岁[IQR，52-72]岁），入住 ICU 时更易发生低氧血症（205/433[47.3%] vs 1322/3491[37.9%]患者需要机械通气，且动脉血氧分压与吸入氧分数比值＜200 mm Hg）。应用逆概率加权后，两组间的基线和疾病严重程度特征均得到很好的平衡。共有 1544 名患者（39.3%）死亡，其中 125 名（28.9%）接受托珠单抗治疗，1419 名（40.6%）未接受托珠单抗治疗。在主要分析中，中位随访 27 天（IQR，14-37）期间，与未接受托珠单抗治疗的患者相比，接受托珠单抗治疗的患者死亡风险较低（HR，0.71；95%CI，0.56-0.92）。托珠单抗治疗组的 30 天死亡率估计为 27.5%（95%CI，21.2%-33.8%），未接受托珠单抗治疗组为 37.1%（95%CI，35.5%-38.7%）（风险差异，9.6%；95%CI，3.1%-16.0%）。
结论和相关性：在本队列研究中，入住 ICU 的 COVID-19 危重症患者中，与未早期使用托珠单抗治疗的患者相比，在 ICU 入院后前两天接受托珠单抗治疗的患者住院死亡率较低。然而，这些发现可能易受无法测量的混杂因素影响，需要来自随机临床试验的进一步研究。
