尼马曲韦/利托那韦片在大型美国医疗体系中治疗早期 COVID-19：一项基于人群的队列研究。

Nirmatrelvir Plus Ritonavir for Early COVID-19 in a Large U.S. Health System : A Population-Based Cohort Study.

机构信息

Brigham and Women's Hospital and Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and Botswana Harvard AIDS Institute, Gaborone, Botswana (S.D.).

Brigham and Women's Hospital, Boston, Massachusetts (A.K., L.D., E.D., L.R.B., A.E.W.).

出版信息

Ann Intern Med. 2023 Jan;176(1):77-84. doi: 10.7326/M22-2141. Epub 2022 Dec 13.

DOI:10.7326/M22-2141

PMID:36508742

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9753458/

Abstract

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

44 551 nonhospitalized 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, 12 541 (28.1%) patients were prescribed nirmatrelvir plus ritonavir, and 32 010 (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 nirmatrelvir plus 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.

PRIMARY FUNDING SOURCE

National Institutes of Health.

摘要

背景

在 EPIC-HR（评估蛋白酶抑制剂对高危人群 COVID-19 的疗效）试验中，奈玛特韦/利托那韦可将未接种疫苗的 COVID-19 早期门诊患者的住院或死亡风险降低 89%。奈玛特韦/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 普遍存在的免疫和免疫逃避 SARS-CoV-2 谱系的情况下，奈玛特韦/利托那韦是否可降低 COVID-19 早期门诊患者的住院或死亡风险。

设计

使用逆概率加权模型分析基于人群的队列研究，以考虑到治疗中预期的偏倚。

设置

一个大型医疗保健系统，在 2022 年奥密克戎波期间（1 月 1 日至 7 月 17 日）为马萨诸塞州和新罕布什尔州的 150 万名患者提供护理。

患者

44551 名未住院的 50 岁及以上成年人（90.3%至少接种了 3 剂疫苗），患有 COVID-19 且无奈玛特韦/利托那韦禁忌证。

测量指标

主要结局是 COVID-19 诊断后 14 天内住院或 28 天内死亡的复合结局。

结果

在研究期间，12541 名（28.1%）患者开具了奈玛特韦/利托那韦处方，32010 名（71.9%）患者未开具。开具奈玛特韦/利托那韦的患者更有可能年龄较大、合并症更多且已接种疫苗。在开具奈玛特韦/利托那韦的 69 名患者（0.55%）和未开具的 310 名患者（0.97%）中，发生了住院或死亡的复合结局（校正风险比，0.56[95%CI，0.42 至 0.75]）。接受奈玛特韦/利托那韦治疗的患者住院风险（校正风险比，0.60[CI，0.44 至 0.81]）和死亡风险（校正风险比，0.29[CI，0.12 至 0.71]）均较低。