Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large US Health System A Population-Based Cohort Study
Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large US Health System A Population-Based Cohort Study
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DOI：
10.7326/m22-2141
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发表时间：
2022-12-13
影响因子：
39.2
通讯作者：
Woolley, Ann E.
中科院分区：
文献类型：
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作者：
Dryden-Peterson, Scott;Kim, Andy;Woolley, Ann E.
背景：在EPIC-HR(高危患者中对新冠肺炎的蛋白酶抑制评估)试验中，尼马瑞韦联合利托那韦使早期新冠肺炎患者中未接种疫苗的门诊患者的住院或死亡减少89%。尼马瑞韦联合利托那韦在接种人群中的临床影响尚不确定。目的：评估在SARS-CoV-2免疫流行和免疫逃逸的背景下，尼马瑞韦联合利托那韦是否降低了早期新冠肺炎门诊患者的住院或死亡风险。设计：对基于人群的队列研究进行分析，以模拟临床试验，使用反向概率加权模型来解释治疗中的预期偏差。环境：一个大型医疗保健系统，在奥米克龙波(2022年1月1日至7月17日)期间，为马萨诸塞州和新罕布夏州的150万名患者提供护理。患者：44551名非住院成人(90.3%接种3剂疫苗)，年龄在50岁或以上，服用新冠肺炎，尼马瑞韦和利托那韦没有禁忌症。测量：主要结果是新冠肺炎确诊后14天内住院或28天内死亡。结果：在研究期间，12541名患者(28.1%)服用了尼马瑞韦和利托那韦，32010名患者(71.9%)没有服用。服用尼马瑞韦和利托那韦的患者更有可能年龄较大，有更多的合并症，并接种疫苗。服用尼马瑞韦和利托那韦的69名患者(0.55%)和未服用尼马瑞韦的310名患者(0.97%)出现住院或死亡的综合结果(调整后的风险比为0.56[95%CI，0.42至0.75])。接受尼马瑞韦加利托那韦治疗的患者住院(调整后的风险比为0.60[CI，0.44至0.81])和死亡(调整后的风险比为0.29[CI，0.12至0.71])较低。限制：由于获得新冠肺炎疫苗、诊断测试和治疗的机会不同，可能存在残余混杂。结论：在门诊诊断为新冠肺炎后，住院或死亡的总体风险已经很低(1%)，但尼马瑞韦联合利托那韦进一步降低了这一风险。
Background: In the EPIC-HR (Evaluation of Protease Inhibition for Covid-19 in High-Risk Patients) trial, nirmatrelvir plus ritonavir led to an 89% reduction in hospitalization or death among unvaccinated outpatients with early COVID-19. The clinical impact of nirmatrelvir plus ritonavir among vaccinated populations is uncertain. Objective: To assess whether nirmatrelvir plus ritonavir reduces risk for hospitalization or death among outpatients with early COVID-19 in the setting of prevalent SARS-CoV-2 immunity and immune-evasive SARS-CoV-2 lineages. Design: Population-based cohort study analyzed to emulate a clinical trial using inverse probability-weighted models to account for anticipated bias in treatment. Setting: A large health care system providing care for 1.5 million patients in Massachusetts and New Hampshire during the Omicron wave (1 January to 17 July 2022). Patients: 44551 non hospitalized adults (90.3% with >= 3 vaccine doses) aged 50 years or older with COVID-19 and no contraindications for nirmatrelvir plus ritonavir. Measurements: The primary outcome was a composite of hospitalization within 14 days or death within 28 days of a COVID-19 diagnosis. Results: During the study period, 12541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32010 (71.9%)were not. Patients prescribed nirmatrelvir plus ritonavir were more likely to be older, have more comorbidities, and be vaccinated. The composite outcome of hospitalization or death occurred in 69 (0.55%) patients who were prescribed nirmatrelvir plus ritonavir and 310 (0.97%) who were not (adjusted risk ratio, 0.56 [95% CI, 0.42 to 0.75]). Recipients of nirmatrelvirplus ritonavir had lower risk for hospitalization (adjusted risk ratio, 0.60 [CI, 0.44 to 0.81]) and death (adjusted risk ratio, 0.29[CI, 0.12 to 0.71]). Limitation: Potential residual confounding due to differential access to COVID-19 vaccines, diagnostic tests, and treatment. Conclusion: The overall risk for hospitalization or death was already low (1%) after an outpatient diagnosis of COVID-19,but nirmatrelvir plus ritonavir reduced this risk further.