Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.
Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.
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DOI：
10.1056/nejmoa2028836
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发表时间：
2020-12-10
期刊：
影响因子：
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通讯作者：
BACC Bay Tocilizumab Trial Investigators
中科院分区：
文献类型：
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作者：
Stone JH;Frigault MJ;Serling-Boyd NJ;Fernandes AD;Harvey L;Foulkes AS;Horick NK;Healy BC;Shah R;Bensaci AM;Woolley AE;Nikiforow S;Lin N;Sagar M;Schrager H;Huckins DS;Axelrod M;Pincus MD;Fleisher J;Sacks CA;Dougan M;North CM;Halvorsen YD;Thurber TK;Dagher Z;Scherer A;Wallwork RS;Kim AY;Schoenfeld S;Sen P;Neilan TG;Perugino CA;Unizony SH;Collier DS;Matza MA;Yinh JM;Bowman KA;Meyerowitz E;Zafar A;Drobni ZD;Bolster MB;Kohler M;D'Silva KM;Dau J;Lockwood MM;Cubbison C;Weber BN;Mansour MK;BACC Bay Tocilizumab Trial Investigators
白细胞介素-6受体阻滞剂在未接受机械通气的2019冠状病毒病（Covid-19）住院患者中的疗效尚不清楚。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型（SARS-CoV-2）感染、炎症过度状态和以下至少两种体征的患者：发热（体温> 38 ° C）、肺浸润或需要补充氧气以维持氧饱和度大于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（每公斤体重8 mg）或安慰剂。主要结局是插管或死亡，在事件发生时间分析中进行评估。次要疗效结局为基线时接受辅助供氧的患者的临床恶化和停止辅助供氧，均在至事件发生时间分析中进行评估。我们招募了243名患者; 141名（58%）为男性，102名（42%）为女性。中位年龄为59.8岁（范围：21.7 - 85.4岁），45%的患者为西班牙裔或拉丁裔。托珠单抗组与安慰剂组相比，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）。在第14天，托珠单抗组18.0%的患者和安慰剂组14.9%的患者出现疾病恶化。托珠单抗组至停止辅助供氧的中位时间为5.0天（95% CI，3.8 - 7.6），安慰剂组为4.9天（95% CI，3.8 - 7.8）（P = 0.69）。第14天，托珠单抗组24.6%的患者和安慰剂组21.2%的患者仍在接受辅助供氧。接受托珠单抗治疗的患者比接受安慰剂治疗的患者发生严重感染的次数少。托珠单抗对预防中度住院的新冠肺炎患者插管或死亡无效。然而，由于疗效比较的置信区间很宽，因此不能排除某些益处或危害。（由Genentech资助; www.example.com编号，NCT 04356937。）
The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear. 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. 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. 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.)