Tocilizumab in patients with severe COVID-19: a retrospective cohort study
Tocilizumab in patients with severe COVID-19: a retrospective cohort study
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DOI：
10.1016/s2665-9913(20)30173-9
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发表时间：
2020-08-01
影响因子：
25.4
通讯作者：
Mussini, Cristina
中科院分区：
文献类型：
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作者：
Guaraldi, Giovanni;Meschiari, Marianna;Mussini, Cristina
背景目前尚无治疗COVID-19肺炎的药物获批。本研究的目的是评估托珠单抗在降低接受标准治疗的严重COVID-19肺炎患者的有创机械通气和死亡风险方面的作用。2月21日至3月24日期间，在意大利博洛尼亚和雷焦艾米利亚的三级医疗中心接受治疗的严重COVID-19肺炎患者（>= 18岁），2020年，以及2020年2月21日至4月30日期间在意大利摩德纳的三级护理中心。所有患者均接受标准治疗（即，辅助供氧、羟氯喹、阿奇霉素、抗逆转录病毒药物和低分子量肝素），非随机选择的患者亚组也接受托珠单抗治疗。托珠单抗以8 mg/kg体重（最大剂量为800 mg）分两次静脉输注给药，间隔12小时，或在静脉制剂不可用时，以162 mg分两次同时皮下给药，每条大腿各一次（即，总计324 mg）。主要终点是有创机械通气或死亡的复合终点。在调整性别、年龄、招募中心、症状持续时间和基线序贯器官衰竭评估（SOFA）评分后，使用Kaplan-Meier曲线和考克斯回归分析对治疗组进行比较。标准治疗组365例患者中有57例（16%）需要机械通气，而托珠单抗治疗组179例患者中有33例（18%）需要机械通气（p=0.41; 88例静脉治疗患者中有16例[18%]，91例皮下治疗患者中有17例[19%]）。标准治疗组有73例（20%）患者死亡，而标准治疗组有13例（7%; p
Background No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment.Methods This retrospective, observational cohort study included adults (>= 18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score.Findings Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0.41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p