Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland.
JAMA Netw Open. 2021 Mar 1;4(3):e213071. doi: 10.1001/jamanetworkopen.2021.3071.
Clinical effectiveness data on remdesivir are urgently needed, especially among diverse populations and in combination with other therapies.
To examine whether remdesivir administered with or without corticosteroids for treatment of coronavirus disease 2019 (COVID-19) is associated with more rapid clinical improvement in a racially/ethnically diverse population.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective comparative effectiveness research study was conducted from March 4 to August 29, 2020, in a 5-hospital health system in the Baltimore, Maryland, and Washington, DC, area. Of 2483 individuals with confirmed severe acute respiratory syndrome coronavirus 2 infection assessed by polymerase chain reaction, those who received remdesivir were matched to infected individuals who did not receive remdesivir using time-invariant covariates (age, sex, race/ethnicity, Charlson Comorbidity Index, body mass index, and do-not-resuscitate or do-not-intubate orders) and time-dependent covariates (ratio of peripheral blood oxygen saturation to fraction of inspired oxygen, blood pressure, pulse, temperature, respiratory rate, C-reactive protein level, complete white blood cell count, lymphocyte count, albumin level, alanine aminotransferase level, glomerular filtration rate, dimerized plasmin fragment D [D-dimer] level, and oxygen device). An individual in the remdesivir group with k days of treatment was matched to a control patient who stayed in the hospital at least k days (5 days maximum) beyond the matching day.
Remdesivir treatment with or without corticosteroid administration.
The primary outcome was rate of clinical improvement (hospital discharge or decrease of 2 points on the World Health Organization severity score), and the secondary outcome, mortality at 28 days. An additional outcome was clinical improvement and time to death associated with combined remdesivir and corticosteroid treatment.
Of 2483 consecutive admissions, 342 individuals received remdesivir, 184 of whom also received corticosteroids and 158 of whom received remdesivir alone. For these 342 patients, the median age was 60 years (interquartile range, 46-69 years), 189 (55.3%) were men, and 276 (80.7%) self-identified as non-White race/ethnicity. Remdesivir recipients had a shorter time to clinical improvement than matched controls without remdesivir treatment (median, 5.0 days [interquartile range, 4.0-8.0 days] vs 7.0 days [interquartile range, 4.0-10.0 days]; adjusted hazard ratio, 1.47 [95% CI, 1.22-1.79]). Remdesivir recipients had a 28-day mortality rate of 7.7% (22 deaths) compared with 14.0% (40 deaths) among matched controls, but this difference was not statistically significant in the time-to-death analysis (adjusted hazard ratio, 0.70; 95% CI, 0.38-1.28). The addition of corticosteroids to remdesivir was not associated with a reduced hazard of death at 28 days (adjusted hazard ratio, 1.94; 95% CI, 0.67-5.57).
In this comparative effectiveness research study of adults hospitalized with COVID-19, receipt of remdesivir was associated with faster clinical improvement in a cohort of predominantly non-White patients. Remdesivir plus corticosteroid administration did not reduce the time to death compared with remdesivir administered alone.
迫切需要有关瑞德西韦临床疗效的数据，尤其是在不同人群中和与其他疗法联合使用的情况下。
检查瑞德西韦联合或不联合皮质类固醇治疗 2019 年冠状病毒病（COVID-19）是否与种族/民族多样化人群更快的临床改善相关。
设计、地点和参与者：这是一项回顾性比较有效性研究，于 2020 年 3 月 4 日至 8 月 29 日在马里兰州巴尔的摩和华盛顿特区的一个 5 家医院的医疗系统中进行。在通过聚合酶链反应评估的 2483 名确诊严重急性呼吸综合征冠状病毒 2 感染患者中，那些接受瑞德西韦治疗的患者与未接受瑞德西韦治疗的感染患者使用时间不变协变量（年龄、性别、种族/民族、Charlson 合并症指数、体重指数和不复苏或不插管医嘱）和时间相关协变量（外周血氧饱和度与吸入氧分数的比值、血压、脉搏、体温、呼吸频率、C 反应蛋白水平、全白细胞计数、淋巴细胞计数、白蛋白水平、丙氨酸氨基转移酶水平、肾小球滤过率、二聚体纤维蛋白碎片 D[D-二聚体]水平和氧设备）进行匹配。瑞德西韦组中接受 k 天治疗的个体与在匹配日至少住院 k 天（最长 5 天）的对照患者相匹配。
瑞德西韦联合或不联合皮质类固醇治疗。
主要结局是临床改善率（出院或世界卫生组织严重程度评分降低 2 分），次要结局是 28 天死亡率。另外的结局是瑞德西韦和皮质类固醇联合治疗与临床改善和死亡时间的关系。
在连续 2483 例入院患者中，342 例接受了瑞德西韦治疗，其中 184 例还接受了皮质类固醇治疗，158 例单独接受了瑞德西韦治疗。对于这 342 名患者，中位年龄为 60 岁（四分位距，46-69 岁），189 名（55.3%）为男性，276 名（80.7%）自认为是非白人种族/民族。与未接受瑞德西韦治疗的匹配对照组相比，接受瑞德西韦治疗的患者达到临床改善的时间更短（中位数，5.0 天[四分位距，4.0-8.0 天]比 7.0 天[四分位距，4.0-10.0 天]；调整后的危险比，1.47[95%CI，1.22-1.79]）。瑞德西韦组患者 28 天死亡率为 7.7%（22 例死亡），而匹配对照组为 14.0%（40 例死亡），但在死亡时间分析中差异无统计学意义（调整后的危险比，0.70；95%CI，0.38-1.28）。瑞德西韦联合皮质类固醇治疗与 28 天死亡风险降低无关（调整后的危险比，1.94；95%CI，0.67-5.57）。
在这项针对 COVID-19 住院成人的比较有效性研究中，瑞德西韦的使用与主要是非白人患者的更快临床改善相关。瑞德西韦联合皮质类固醇治疗与单独使用瑞德西韦相比，并未降低死亡时间。
