ARTICLES| VOLUME 400, ISSUE 10359, P1213-1222, OCTOBER 08, 2022
Real-world effectiveness of molnupiravir and nirmatrelvir plus ritonavir against mortality, hospitalisation, and in-hospital outcomes among community-dwelling, ambulatory patients with confirmed SARS-CoV-2 infection during the omicron wave in Hong Kong: an observational study
Carlos K H Wong, Ivan C H Au, Kristy T K Lau, et al
Lancet 2022; 400: 1213-1222 Published:October 08, 2022
DOI:https://doi.org/10.1016/S0140-6736(22)01586-0
Summary
Background
Little is known about the real-world effectiveness of oral antivirals against the SARS-CoV-2 omicron (B.1.1.529) variant. We aimed to assess the clinical effectiveness of two oral antiviral drugs among community-dwelling COVID-19 outpatients in Hong Kong.
背景 口服抗病毒藥物對 SARS-COV-2 omicron (B.1.1.529)亞型 BA.2.2 的真實世界療效知之甚 少。我們的目的是評估兩種口服抗病毒藥物在香港社區居住的新冠肺炎門診患者中的臨床效果。
Methods
In this observational study, we used data from the Hong Kong Hospital Authority to identify an unselected, territory-wide cohort of non-hospitalised patients with an officially registered diagnosis of SARS-CoV-2 infection between Feb 26 and June 26, 2022, during the period in which the omicron subvariant BA.2.2 was dominant in Hong Kong. We used a retrospective cohort design as primary analysis, and a case-control design as sensitivity analysis. We identified patients with COVID-19 who received either molnupiravir (800 mg twice daily for 5 days) or nirmatrelvir plus ritonavir (nirmatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days, or nirmatrelvir 150 mg and ritonavir 100 mg if estimated glomerular filtration rate was 30–59 mL/min per 1·73 m2). Outpatient oral antiviral users were matched with controls using propensity score (1:10) according to age, sex, date of SARS-CoV-2 infection diagnosis, Charlson Comorbidity Index score, and vaccination status. Study outcomes were death, COVID-19-related hospitalisation, and in-hospital disease progression (in-hospital death, invasive mechanical ventilation, or intensive care unit admission). Hazard ratios (HRs) were estimated by Cox regression for the primary analysis, and odds ratios in oral antiviral users compared with non-users by logistic regression for the sensitivity analysis.
方法 在這項觀察性研究中，我們使用了香港醫院管理局的數據，識別了一組在 2022 年 2 月 26 日 至 6 月 26 日，Omicron 亞型 BA.2.2 在香港占主導地位的期間，正式登記為新冠肺炎感染的非住 院患者。我們採用回顧性隊列設計作為主要分析，并採用病例對照設計作為敏感性分析。我們納 入了接受莫努匹韋或帕昔洛韋治療的新冠肺炎患者。根據年齡、性別、新冠肺炎診斷日期、 Charlson 共病指數評分和疫苗接種狀態，使用 1 比 10 傾向評分匹配法將使用口服抗病毒藥物的 門診患者與對照組進行匹配。研究事件是死亡、與新冠肺炎相關的住院和院内疾病進展(院内死 亡、入侵式呼吸器治療或入住深切治療部病房)。 Cox 回歸估計了 HR (風險比)， logistic 回歸 估計了口服抗病毒藥物組與非口服抗病毒藥物組的優勢比。
Findings
Among 1 074 856 non-hospitalised patients with COVID-19, 5383 received molnupiravir and 6464 received nirmatrelvir plus ritonavir in the community setting. Patients were followed up for a median of 103 days in the molnupiravir group and 99 days in the nirmatrelvir plus ritonavir group. Compared with nirmatrelvir plus ritonavir users, those on molnupiravir were older (4758 [85·9%] vs 4418 [88.7%] aged >60 years) and less likely to have been fully vaccinated (1850 [33·4%] vs 800 [16·1%]). Molnupiravir use was associated with lower risks of death (HR 0·76 [95% CI 0·61–0·95]) and in-hospital disease progression (0·57 [0·43–0·76]) than non-use was, whereas risk of hospitalisation was similar in both groups (0·98 [0·89–1·06]). Nirmatrelvir plus ritonavir use was associated with lower risks of death (0·34 [0·22–0·52]), hospitalisation (0·76 [0·67–0·86]), and in-hospital disease progression (0·57 [0·38–0·87]) than non-use was. We consistently found reduced risks of mortality and hospitalisation associated with early oral antiviral use among older patients. The findings from the case-control analysis broadly supported those from the primary analysis.
結果 在 1074856 例未住院的新冠肺炎患者中，5383 例在社區接受了莫努匹韋治療，6464 例在社 區接受了帕昔洛韋治療。 莫努匹韋組和帕昔洛韋組患者的中位隨訪時間分別為 103 天和 99 天。 與帕昔洛韋相比，使用莫努匹韋的患者年齡更大(年齡 > 60 歲: 4758 例 [85.9%]與 4418 例[88.7%] 相比)，而且完全接種疫苗的可能性更小(1850 例[33% 4%]與 800 例[16.1%]相比)。與不使用莫 努匹韋相比，使用莫努匹韋的死亡率(HR=0.76， 95%CI=0.61-0.95)和院内疾病進展 (HR=0.57， 95%CI=0.43-0.76)較低，而兩組住院風險相似(HR=0.98，95%CI=0.89-1.06)。與 未使用相比，使用帕昔洛韋的死亡風險(HR=0.34， 95%CI=0.22- 0.52)、住院風險(HR=0.76， 95%CI=0.67-0.86)和院内疾病進展風險(HR=0.57， 95%CI=0.38-0.87)較低。在老年患者中，我 們一致發現早期口服抗病毒藥物可降低死亡率和住院風險。病例對照分析的結果廣泛支持主要分 析的結果。
Interpretation
During Hong Kong's wave of SARS-CoV-2 omicron subvariant BA.2.2, among non-hospitalised patients with COVID-19, early initiation of novel oral antivirals was associated with reduced risks of mortality and in-hospital disease progression. Nirmatrelvir plus ritonavir use was additionally associated with a reduced risk of hospitalisation.
結論 在香港 SARS-COV-2 Omicron 亞型 BA.2.2 的流行期間，非住院的新冠肺炎患者早期開始使 用口服抗病毒藥物與降低死亡率和院内疾病進展風險相關。此外，使用帕昔洛韋與住院風險降低 相關。
Funding
Health and Medical Research Fund, Health Bureau, Government of Hong Kong Special Administrative Region, China.
