From Massachusetts General Hospital (J.H.S., M.J.F., N.J.S.-B., A.D.F., L.H., A.S.F., N.K.H., B.C.H., C.A.S., M.D., C.M.N., Y.-D.H., T.K.T., Z.D., A.S., R.S.W., A.Y.K., S.S., P.S., T.G.N., C.A.P., S.H.U., D.S.C., M.A.M., J.M.Y., K.A.B., E.M., A.Z., Z.D.D., M.B.B., M.K., K.M.D., J.D., M.M.L., M.K.M.), Brigham and Women's Hospital (A.E.W., S.N., B.N.W.), and Boston Medical Center (N.L., M.S.), Boston, North Shore Medical Center, Salem (R.S., A.M.B., C.C.), Newton-Wellesley Hospital, Newton (H.S., D.S.H.), Beth Israel Lahey Health, Burlington (M.A., M.D.P.), and St. Elizabeth's Medical Center, Brighton (J.F.) - all in Massachusetts.
N Engl J Med. 2020 Dec 10;383(24):2333-2344. doi: 10.1056/NEJMoa2028836. Epub 2020 Oct 21.
BACKGROUND: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. METHODS: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo. The primary outcome was intubation or death, assessed in a time-to-event analysis. The secondary efficacy outcomes were clinical worsening and discontinuation of supplemental oxygen among patients who had been receiving it at baseline, both assessed in time-to-event analyses. RESULTS: We enrolled 243 patients; 141 (58%) were men, and 102 (42%) were women. The median age was 59.8 years (range, 21.7 to 85.4), and 45% of the patients were Hispanic or Latino. The hazard ratio for intubation or death in the tocilizumab group as compared with the placebo group was 0.83 (95% confidence interval [CI], 0.38 to 1.81; P = 0.64), and the hazard ratio for disease worsening was 1.11 (95% CI, 0.59 to 2.10; P = 0.73). At 14 days, 18.0% of the patients in the tocilizumab group and 14.9% of the patients in the placebo group had had worsening of disease. The median time to discontinuation of supplemental oxygen was 5.0 days (95% CI, 3.8 to 7.6) in the tocilizumab group and 4.9 days (95% CI, 3.8 to 7.8) in the placebo group (P = 0.69). At 14 days, 24.6% of the patients in the tocilizumab group and 21.2% of the patients in the placebo group were still receiving supplemental oxygen. Patients who received tocilizumab had fewer serious infections than patients who received placebo. CONCLUSIONS: Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19. Some benefit or harm cannot be ruled out, however, because the confidence intervals for efficacy comparisons were wide. (Funded by Genentech; ClinicalTrials.gov number, NCT04356937.).
背景：对于未接受机械通气的 2019 年冠状病毒病（COVID-19）住院患者，白细胞介素 6 受体阻滞剂的疗效尚不清楚。
方法：我们进行了一项随机、双盲、安慰剂对照试验，纳入了确诊为严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染、高炎症状态且至少有以下两种体征的患者：发热（体温>38°C）、肺部浸润或需要补充氧气以维持血氧饱和度大于 92%。患者以 2:1 的比例随机分配接受标准治疗加单剂量托珠单抗（8 毫克/千克体重）或安慰剂。主要结局是气管插管或死亡，采用时间事件分析进行评估。次要疗效结局是基线时接受补充氧气的患者的临床恶化和停止补充氧气，均采用时间事件分析进行评估。
结果：我们共纳入 243 例患者；141 例（58%）为男性，102 例（42%）为女性。中位年龄为 59.8 岁（范围为 21.7 至 85.4），45%的患者为西班牙裔或拉丁裔。托珠单抗组与安慰剂组气管插管或死亡的风险比为 0.83（95%置信区间[CI]，0.38 至 1.81；P=0.64），疾病恶化的风险比为 1.11（95%CI，0.59 至 2.10；P=0.73）。在 14 天时，托珠单抗组 18.0%的患者和安慰剂组 14.9%的患者病情恶化。托珠单抗组停止补充氧气的中位时间为 5.0 天（95%CI，3.8 至 7.6），安慰剂组为 4.9 天（95%CI，3.8 至 7.8）（P=0.69）。在 14 天时，托珠单抗组 24.6%的患者和安慰剂组 21.2%的患者仍在接受补充氧气。接受托珠单抗治疗的患者比接受安慰剂的患者发生严重感染的情况更少。
结论：托珠单抗对预防 COVID-19 中度住院患者的气管插管或死亡无效。然而，由于疗效比较的置信区间较宽，一些获益或危害尚不能排除。（由罗氏公司资助；ClinicalTrials.gov 编号，NCT04356937）。
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