■Nirmatrelvir-利托那韦用于患有2019年冠状病毒病(COVID-19)的正常或轻度肾功能损害(eGFR≥30ml/min/1.73m2)的患者。关于其在晚期肾病中的应用的数据有限(eGFR<30ml/min/1.73m2)。我们进行了一项回顾性观察性研究,评估了尼马特雷韦-利托那韦与莫诺比拉韦治疗COVID-19晚期肾病患者的安全性和有效性。
我们使用来自全域电子健康记录数据库的数据,对年龄≥18岁的晚期肾脏疾病(eGFR<30ml/min/1.73m2)的合格患者进行了目标试验模拟,这些患者在2022年3月16日至31日期间感染了COVID-19并在感染后五天内服用了莫诺比拉韦或尼马特雷韦-利托那韦。基于基线协变量,包括年龄,性别,接受的COVID-19疫苗剂量,Charlson合并症指数(CCI),住院治疗,eGFR,肾脏替代疗法,合并症(癌症,呼吸道疾病,心肌梗塞,缺血性中风,糖尿病,高血压),和药物使用(肾素-血管紧张素系统药物,β受体阻滞剂,钙通道阻滞剂,利尿剂,硝酸盐,降脂药,胰岛素,口服抗糖尿病药物,抗血小板,免疫抑制剂,皮质类固醇,质子泵抑制剂,组胺H2受体拮抗剂,单克隆抗体输注)在过去90天内。从索引日期到最早的结果发生,对个人进行了随访,死亡,从索引日期或数据可用性结束之日起90天。用基线协变量调整的分层Cox比例风险回归用于比较尼马特雷韦-利托那韦接受者和莫诺比拉韦接受者之间的结局风险,包括(i)全因死亡率,(ii)重症监护病房(ICU)入院,(iii)通气支持,(iv)住院,(v)肝功能损害,(vi)缺血性中风,和(七)心肌梗塞。亚组分析包括年龄(<70岁;≥70岁);性别,Charlson合并症指数(≤5;>5),和接受的COVID-19疫苗剂量(0-1;≥2剂)。
■共纳入4886例患者(尼马特雷韦-利托那韦:1462;莫诺比拉韦:3424)。有347个事件的全因死亡率(nirmatrelvir-ritonavir:74,5.06%;molnupiravir:273,7.97%),ICU入院的10个事件(nirmatrelvir-ritonavir:4,0.27%;molnupiravir:6,0.18%),48例通气支持事件(尼马特雷韦-利托那韦:13,0.89%;莫诺比拉韦:35,1.02%),836例住院事件(nirmatrelvir-ritonavir:218,23.98%;molnupiravir:618,28.14%),1例肝损害事件(尼马特雷韦-利托那韦:0,0%;莫诺比拉韦:1,0.03%),缺血性卒中事件8例(尼马特雷韦-利托那韦:3,0.22%;莫诺比拉韦:5,0.16%)和心肌梗死事件9例(尼马特雷韦-利托那韦:2,0.15%;莫诺比拉韦:7,0.22%)。Nirmatrelvir-ritonavir使用者的全因死亡率较低(90天绝对风险降低(ARR)2.91%,95%CI:1.47-4.36%)和住院(90天ARR4.16%,95%CI:0.81-7.51%)与莫努普拉韦用户相比。ICU入院率相似(90天ARR-0.09%,95%CI:-0.4至0.2%),通气支持(90天ARR0.13%,95%CI:-0.45至0.72%),肝功能损害(90天时的ARR为0.03%,95%CI:-0.03至0.09%),缺血性卒中(90天ARR-0.06%,95%CI:-0.35至0.22%),和心肌梗死(90天的ARR0.07%,95%CI:-0.19至0.33%)在尼马特雷韦-利托那韦和莫诺比拉韦使用者之间发现。根据基线特征调整后的相对风险观察到一致的结果。Nirmatrelvir-ritonavir与全因死亡率(HR:0.624,95%CI:0.455-0.857)和住院(HR:0.782,95%CI:0.64-0.954)的风险显着降低相关。
与莫诺比拉韦相比,接受尼马特雷韦-利托那韦治疗的COVID-19晚期肾病患者的全因死亡率和入院率较低。两个治疗组的其他不良临床结果相似。
■健康与医学研究基金(COVID1903010),卫生局,香港特别行政区政府,中国。
UNASSIGNED: Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30 ml/min per 1.73 m2). There is limited data regarding its use in advanced kidney disease (eGFR <30 ml/min per 1.73 m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with
molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease.
UNASSIGNED: We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30 ml/min per 1.73 m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses).
UNASSIGNED: A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462;
molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%;
molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%;
molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%;
molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%;
molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days -0.09%, 95% CI: -0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI: -0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI: -0.03 to 0.09%), ischaemic stroke (ARR at 90 days -0.06%, 95% CI: -0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI: -0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954).
UNASSIGNED: Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups.
UNASSIGNED: Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.