韩国全国靶向试验模拟评估口服抗新冠病毒药物的临床疗效。

Nationwide Target Trial Emulation Evaluating the Clinical Effectiveness of Oral Antivirals for COVID-19 in Korea.

机构信息

Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Public Health Sciences, School of Medicine, University of Connecticut, Storrs, CT, USA.

出版信息

J Korean Med Sci. 2024 Nov 4;39(42):e272. doi: 10.3346/jkms.2024.39.e272.

DOI:10.3346/jkms.2024.39.e272

PMID:39497563

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11538573/

Abstract

BACKGROUND

Despite the proven effectiveness of oral antivirals against severe acute respiratory syndrome coronavirus 2 in randomized trials, their clinical reevaluation is vital in the context of widespread immunity and milder prevalent variants. This study aimed to assess the effectiveness of oral antivirals for coronavirus disease 2019 (COVID-19).

METHODS

This retrospective cohort study utilized a target trial emulation framework to analyze patients with COVID-19 aged 60+ from January to December 2022. Data were obtained from the Korea Disease Control and Prevention Agency and Health Insurance Review and Assessment Service. The study involved 957,036 patients treated with nirmatrelvir/ritonavir and 243,360 treated with molnupiravir, each compared with the matched control groups. Primary outcome was progression to critical COVID-19 requiring advanced respiratory support. Secondary outcomes included progression to severe COVID-19, need for supplemental oxygen, and death within 30 days of the onset of COVID-19. Number needed to treat (NNT) derived from the absolute risk reduction.

RESULTS

Nirmatrelvir/ritonavir was significantly associated with a reduced risk of severe (adjusted odds ratio [aOR], 0.823; 95% confidence interval [CI], 0.803-0.843), critical (aOR, 0.560; 95% CI, 0.503-0.624), and fatal COVID-19 (aOR, 0.694; 95% CI, 0.647-0.744). Similarly, molnupiravir reduced the risk of severe (aOR, 0.895; 95% CI, 0.856-0.937), critical (aOR, 0.672; 95% CI, 0.559-0.807), and fatal cases (aOR, 0.679; 95% CI, 0.592-0.779). NNTs for nirmatrelvir/ritonavir were 203.71 (severe), 1,230.12 (critical), and 691.50 (death); for molnupiravir, they were 352.70 (severe), 1,398.62 (critical), and 862.98 (death). Higher effectiveness was associated with older adults, unvaccinated individuals, and the late pandemic phase.

CONCLUSION

Nirmatrelvir/ritonavir and molnupiravir are effective in preventing progression to severe disease in elderly adults with COVID-19.

摘要

背景

尽管口服抗病毒药物在随机试验中已被证明对严重急性呼吸综合征冠状病毒 2 有效，但在广泛免疫和更温和的流行变异的背景下，对其进行临床重新评估至关重要。本研究旨在评估口服抗病毒药物治疗 2019 年冠状病毒病（COVID-19）的效果。

方法

本回顾性队列研究利用目标试验模拟框架，分析了 2022 年 1 月至 12 月期间年龄在 60 岁及以上的 COVID-19 患者。数据来自韩国疾病控制和预防局以及健康保险审查和评估服务。研究涉及 957,036 例接受奈玛特韦/利托那韦治疗和 243,360 例接受莫努匹韦治疗的患者，每组均与匹配的对照组进行比较。主要结局是进展为需要高级呼吸支持的严重 COVID-19。次要结局包括进展为严重 COVID-19、需要补充氧气以及 COVID-19 发病后 30 天内死亡。从绝对风险降低中得出需要治疗的人数（NNT）。

结果

奈玛特韦/利托那韦显著降低了严重（调整后的优势比[aOR]，0.823；95%置信区间[CI]，0.803-0.843）、危急（aOR，0.560；95%CI，0.503-0.624）和致命 COVID-19（aOR，0.694；95%CI，0.647-0.744）的风险。同样，莫努匹韦降低了严重（aOR，0.895；95%CI，0.856-0.937）、危急（aOR，0.672；95%CI，0.559-0.807）和致命病例（aOR，0.679；95%CI，0.592-0.779）的风险。奈玛特韦/利托那韦的 NNT 为 203.71（严重）、1,230.12（危急）和 691.50（死亡）；莫努匹韦的 NNT 为 352.70（严重）、1,398.62（危急）和 862.98（死亡）。更高的有效性与老年人、未接种疫苗的个体和大流行后期有关。