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Article: Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study
Title | Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study |
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Authors | |
Keywords | Molnupiravir Nirmatrelvir-ritonavir SARS-CoV-2 Viral disease |
Issue Date | 1-Jul-2023 |
Publisher | Elsevier |
Citation | EClinicalMedicine, 2023, v. 64 How to Cite? |
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. Funding: HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government; Collaborative Research Fund, University Grants Committee, the HKSAR Government; and Research Grant from the Food and Health Bureau, the HKSAR Government; the Laboratory of Data Discovery for Health (D4H) funded by the AIR@InnoHK administered by Innovation and Technology Commission. |
Persistent Identifier | http://hdl.handle.net/10722/338380 |
ISSN | 2023 Impact Factor: 9.6 2023 SCImago Journal Rankings: 3.522 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Wan, EYF | - |
dc.contributor.author | Yan, VKC | - |
dc.contributor.author | Wong, ZCT | - |
dc.contributor.author | Chui, CSL | - |
dc.contributor.author | Lai, FTT | - |
dc.contributor.author | Li, X | - |
dc.contributor.author | Wong, CKH | - |
dc.contributor.author | Hung, IFN | - |
dc.contributor.author | Lau, CS | - |
dc.contributor.author | Wong, ICK | - |
dc.contributor.author | Chan, EWY | - |
dc.date.accessioned | 2024-03-11T10:28:25Z | - |
dc.date.available | 2024-03-11T10:28:25Z | - |
dc.date.issued | 2023-07-01 | - |
dc.identifier.citation | EClinicalMedicine, 2023, v. 64 | - |
dc.identifier.issn | 2589-5370 | - |
dc.identifier.uri | http://hdl.handle.net/10722/338380 | - |
dc.description.abstract | <p>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. Funding: HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government; Collaborative Research Fund, University Grants Committee, the HKSAR Government; and Research Grant from the Food and Health Bureau, the HKSAR Government; the Laboratory of Data Discovery for Health (D<sup/>4H) funded by the AIR@InnoHK administered by Innovation and Technology Commission.</p> | - |
dc.language | eng | - |
dc.publisher | Elsevier | - |
dc.relation.ispartof | EClinicalMedicine | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Molnupiravir | - |
dc.subject | Nirmatrelvir-ritonavir | - |
dc.subject | SARS-CoV-2 | - |
dc.subject | Viral disease | - |
dc.title | Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.eclinm.2023.102225 | - |
dc.identifier.scopus | eid_2-s2.0-85171449345 | - |
dc.identifier.volume | 64 | - |
dc.identifier.eissn | 2589-5370 | - |
dc.identifier.isi | WOS:001084387500001 | - |
dc.identifier.issnl | 2589-5370 | - |