Choi, Ming Hong, Wan, Eric Yuk Fai, Wong, Ian Chi Kei, Chan, Esther Wai Yin, Chu, Wing Ming, Tam, Anthony Raymond, Yuen, Kwok Yung and Hung, Ivan Fan Ngai (2024). Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study:a target trial emulation study. The Lancet Infectious Diseases ,
Abstract
Background: Remdesivir (Veklury, Gilead Sciences, Foster City, CA, USA) and nirmatrelvir–ritonavir (Paxlovid, Pfizer, New York, NY, USA) were reported to improve the outcome of patients with mild-to-moderate COVID-19 symptoms. Preclinical data suggest that nirmatrelvir–ritonavir might be more effective than remdesivir alone or in combination with nirmatrelvir–ritonavir for people at high risk of severe COVID-19. We aimed to assess the safety and effectiveness of combining remdesivir and nirmatrelvir–ritonavir compared with using each drug alone for adults hospitalised with COVID-19. Methods: In this target trial emulation study, we used electronic health records of patients aged 18 years or older who received either combination treatment of nirmatrelvir–ritonavir and remdesivir or monotherapy of either drug between March 16 and Dec 31, 2022, within 5 days of hospitalisation for COVID-19 in Hong Kong. Inverse probability of treatment weighting was applied to balance baseline patient characteristics across the treatment groups. The primary outcome was all-cause mortality. Cox proportional hazards regression adjusting weighting was used to compare the risk of all-cause mortality, intensive care unit (ICU) admission, or ventilatory support for 90 days of follow-up between groups. Findings: Between March 16 and Dec 31, 2022, 18 196 participants were identified from electronic health records and assigned to receive remdesivir (n=4232), nirmatrelvir–ritonavir (n=13 656), or nirmatrelvir–ritonavir and remdesivir (n=308). By applying an inverse probability of treatment weighting, a weighted sample composed of 18 410 recipients of nirmatrelvir–ritonavir and remdesivir combination treatment, 18 178 recipients of remdesivir monotherapy, and 18 287 recipients of nirmatrelvir–ritonavir monotherapy was obtained. After a median follow-up of 84 days (IQR 45–90), risk of mortality was lower in patients who received nirmatrelvir–ritonavir monotherapy (hazard ratio [HR] 0·18 [95% CI 0·15 to 0·20]; absolute risk reduction [ARR] –16·33% [95% CI –16·98 to –15·68]) or remdesivir and nirmatrelvir–ritonavir combination therapy (HR 0·66 [95% CI 0·49 to 0·89]; ARR –6·52% [95% CI –7·29 to –5·74]) than in patients who received remdesivir monotherapy. Similar results were observed for ICU admission or ventilatory support (nirmatrelvir–ritonavir monotherapy: HR 0·09 [95% CI 0·07 to 0·11]; ARR –10·04% [95% CI –10·53 to –9·56]; combination therapy: HR 0·68 [95% CI 0·42 to 1·12]; ARR –3·24% [95% CI –3·84 to –2·64]). Compared with combination therapy, nirmatrelvir–ritonavir monotherapy was associated with lower risk of mortality (HR 0·27 [95% CI 0·20 to 0·37]; ARR –9·81% [95% CI –10·39 to –9·24]) and ICU admission or ventilatory support (HR 0·13 [95% CI 0·08 to 0·22]; ARR –6·80% [95% CI –7·22 to –6·39]). Interpretation: Our study highlighted the potential for reduced risk of mortality, ICU admission, or the need for ventilatory support in patients hospitalised with COVID-19 treated with nirmatrelvir–ritonavir as a monotherapy compared with treatment regimens based on nirmatrelvir–ritonavir and remdesivir combination therapy or remdesivir monotherapy. Further randomised controlled trials are needed to support the validity of the current results.
Publication DOI: | https://doi.org/10.1016/S1473-3099(24)00353-0 |
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Divisions: | College of Health & Life Sciences > Aston Pharmacy School |
Funding Information: | The authors gratefully acknowledge the Centre for Health Protection, the Department of Health, and the Hospital Authority for facilitating data access. They would like to express their gratitude to Boyuan Wang and Vivian Yahui Xu for their programming sup |
Additional Information: | Copyright © 2024 Elsevier Ltd. This manuscript version is made available under the CC-BY-NC-ND 4.0 license (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
Uncontrolled Keywords: | Infectious Diseases |
Publication ISSN: | 1474-4457 |
Data Access Statement: | Data will not be available for others as the data custodians have not given permission. Academic institutions, government departments, or non-governmental organisations in Hong Kong can apply for the access to data through the Hospital Authority’s data sharing portal (https://www3.ha.org.hk/data). |
Last Modified: | 12 Aug 2024 17:05 |
Date Deposited: | 07 Aug 2024 15:13 |
Full Text Link: |
https://www.sci ... 473309924003530 |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2024-07-15 |
Published Online Date: | 2024-07-15 |
Accepted Date: | 2024-05-21 |
Authors: |
Choi, Ming Hong
Wan, Eric Yuk Fai Wong, Ian Chi Kei ( ![]() Chan, Esther Wai Yin Chu, Wing Ming Tam, Anthony Raymond Yuen, Kwok Yung Hung, Ivan Fan Ngai |
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