Wan, Eric Yuk Fai, Yan, Vincent Ka Chun, Wong, Zoey Cho Ting, Chui, Celine Sze Ling, Lai, Francisco Tsz Tsun, Li, Xue, Wong, Carlos King Ho, Hung, Ivan Fan Ngai, Lau, Chak Sing, Wong, Ian Chi Kei and Chan, Esther Wai Yin (2023). Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study. EClinicalMedicine, 64 ,
Abstract
BACKGROUND: Molnupiravir and nirmatrelvir-ritonavir have emerged as promising options for COVID-19 treatment, but direct comparisons of their effectiveness have been limited. This study aimed to compare the effectiveness of these two oral antiviral drugs in non-hospitalised and hospitalised patients with COVID-19. METHODS: In this target trial emulation study, we used data from a territory-wide electronic health records database on eligible patients aged ≥18 years infected with COVID-19 who were prescribed either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16 March 2022 and 31 December 2022 in the non-hospitalised and hospitalised settings in Hong Kong. A sequence trial approach and 1:1 propensity score matching was applied based on age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index, comorbidities, and drug use within past 90 days. Cox regression adjusted with patients' characteristics was used to compare the risk of effectiveness outcomes (all-cause mortality, intensive care unit (ICU) admission or ventilatory support and hospitalisation) between groups. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (<4; ≥4), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). FINDINGS: A total of 63,522 non-hospitalised (nirmatrelvir-ritonavir: 31,761; molnupiravir: 31,761) and 11,784 hospitalised (nirmatrelvir-ritonavir: 5892; molnupiravir: 5892) patients were included. In non-hospitalised setting, 336 events of all-cause mortality (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 265, 0.83%), 162 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 91, 0.29%), and 4890 events of hospitalisation (nirmatrelvir-ritonavir: 1853, 5.83%; molnupiravir: 3037, 9.56%) were observed. Lower risks of all-cause mortality (absolute risk reduction (ARR) at 28 days: 0.61%, 95% CI: 0.50-0.72; HR: 0.43, 95% CI: 0.33-0.56) and hospital admission (ARR at 28 days: 3.73%, 95% CI: 3.31-4.14; HR: 0.72, 95% CI: 0.67-0.76) were observed in nirmatrelvir-ritonavir users compared to molnupiravir users. In hospitalised setting, 509 events of all-cause mortality (nirmatrelvir-ritonavir: 176, 2.99%; molnupiravir: 333, 5.65%), and 50 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 26, 0.44%; molnupiravir: 24, 0.41%) were observed. Risk of all-cause mortality was lower for nirmatrelvir-ritonavir users than for molnupiravir users (ARR at 28 days: 2.66%, 95% CI: 1.93-3.40; HR: 0.59, 95% CI: 0.49-0.71). In both settings, there was no difference in the risk of intensive care unit admission or ventilatory support between groups. The findings were consistent across all subgroup's analyses. INTERPRETATION: Our analyses suggest that nirmatrelvir-ritonavir was more effective than molnupiravir in reducing the risk of all-cause mortality in both non-hospitalised and hospitalised patients. When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option.
Publication DOI: | https://doi.org/10.1016/j.eclinm.2023.102225 |
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Divisions: | College of Health & Life Sciences > Aston Pharmacy School |
Funding Information: | This study was funded by HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government (Principal Investigator (WP2): EWYC; Ref No. COVID1903011); Collaborative Research Fund, University Grants Committee, the HKSAR Government ( |
Additional Information: | Copyright © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
Uncontrolled Keywords: | SARS-CoV2,Viral disease,Molnupiravir,Nirmatrelvir-Ritonavir |
Publication ISSN: | 2589-5370 |
Data Access Statement: | Data are not available, as the data custodians (the Hospital Authority and the Department of Health of Hong Kong SAR) have not given permission for sharing due to patient confidentiality and privacy concerns. Local academic institutions, government departments, or nongovernmental organizations may apply for the access to data through the Hospital Authority’s data sharing portal (https://www3.ha.org.hk/data). |
Last Modified: | 06 Aug 2024 10:02 |
Date Deposited: | 19 Jul 2024 16:45 |
Full Text Link: | |
Related URLs: |
https://www.sci ... 589537023004029
(Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2023-10 |
Published Online Date: | 2023-09-20 |
Accepted Date: | 2023-09-05 |
Authors: |
Wan, Eric Yuk Fai
Yan, Vincent Ka Chun Wong, Zoey Cho Ting Chui, Celine Sze Ling Lai, Francisco Tsz Tsun Li, Xue Wong, Carlos King Ho Hung, Ivan Fan Ngai Lau, Chak Sing Wong, Ian Chi Kei ( ![]() Chan, Esther Wai Yin |
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