دورية أكاديمية
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.
| العنوان: | 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. |
|---|---|
| المؤلفون: | Choi MH; Division of Infectious Diseases, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China., Wan EYF; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China; Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China., Wong ICK; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China; Aston Pharmacy School, Aston University, Birmingham, UK; School of Pharmacy, Medical Sciences Division, Macau University of Science and Technology, Macau Special Administrative Region, China., Chan EWY; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China; Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China., Chu WM; Division of Infectious Diseases, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China., Tam AR; Division of Infectious Diseases, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China., Yuen KY; State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China., Hung IFN; Division of Infectious Diseases, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: ivanhung@hku.hk. |
| المصدر: | The Lancet. Infectious diseases [Lancet Infect Dis] 2024 Jul 15. Date of Electronic Publication: 2024 Jul 15. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-4457 (Electronic) Linking ISSN: 14733099 NLM ISO Abbreviation: Lancet Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001- |
| مستخلص: | 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. Funding: The Health and Medical Research Fund Commissioned Research on COVID-19. Translation: For the Chinese translation of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests EYFW has received research grants from the Food and Health Bureau of the Hong Kong Government, the Hong Kong Research Grants Council of the Hong Kong Government, Narcotics Division, Security Bureau of the Hong Kong Government, and National Natural Science Foundation of China, outside the submitted work. ICKW reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council of the Hong Kong Government, the Hong Kong Health and Medical Research Fund, the UK National Institute for Health Research, the European Commission, and the Australia National Health and Medical Research Council; reports consulting fees from IQVIA and WHO; reports payment for expert testimony for Appeal Court of Hong Kong; is a non-executive director of Jacobson Medical in Hong Kong, Advance Data Analytics for Medical Science (in Hong Kong), Asia Medicine Regulatory Affairs Services, and OCUS Innovation (in Hong Kong, Ireland, and the UK); is a former director of Therakind in the UK, outside of the submitted work; and reports being a member of the Pharmacy and Poisons Board in Hong Kong, the Expert Committee on Clinical Events Assessment Following COVID-19 Immunisation, and the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government. EWYC reports grants from the Hong Kong Research Grants Council of the Hong Kong Government, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Foundation of China, Wellcome Trust, Bayer, Bristol Myers Squibb, Pfizer, Janssen, Amgen, Takeda, RGA Reinsurance Company, AstraZeneca, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, Innovation and Technology Commission of the Hong Kong Government, Novartis, and the Australia National Health and Medical Research Council, and honorarium from Hospital Authority, outside the submitted work. KYY is a shareholder of the Hong Kong Universal Biologicals Company and Hong Kong Universal Vaccine; reports and collaborating with Sinovac Biotech and the China National Pharmaceutical Group (Sinopharm); reports grants from Health@InnoHK, Innovation and Technology Commission of the Hong Kong Government, the Theme-Based Research Scheme (T11-709/21-N), Research Grants Council of the Hong Kong Government, Programme of Enhancing Laboratory Surveillance and Investigation of Emerging Infectious Diseases and Antimicrobial Resistance for the Hong Kong Department of Health, the China National Key Research and Development Program (projects 2021YFC0866100 and 2023YFC3041600), Sanming Project of Medicine in Shenzhen, China (SZSM201911014), the High Level-Hospital Program, Health Commission of Guangdong Province, China, and the Emergency Collaborative Project of Guangzhou Laboratory (EKPG22-01); and donations from the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, Michael Seak-Kan Tong, May Tam Mak Mei Yin, Providence Foundation (in memory of the late Lui Hac Minh), Lee Wan Keung Charity Foundation, Hong Kong Sanatorium & Hospital, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund, The Chen Wai Wai Vivien Foundation, Chan Yin Chuen Memorial Charitable Foundation, Tse Kam Ming Laurence, Marina Man-Wai Lee, the Hong Kong Hainan Commercial Association South China Microbiology Research Fund, Pui-Sze Cheng, Perfect Shape Medical, Kai Chong Tong, Tse Kam Ming Laurence, Foo Oi Foundation, Betty Hing-Chu Lee, and Ping Cham So. IFNH is an advisory board member for Pfizer, MSD, GSK, Moderna, and Sinopharm; has received research grants from the Hong Kong Research Grants Council and the Hong Kong Health and Medical Research Fund; has received a travel grant from MSD and AstraZeneca to attend scientific meetings; reports a role as a co-convenor of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunisation; is a member of the COVID-19 Expert Advisory Panel of the Hong Kong Government, the advisory panel on COVID-19 Vaccines of the Hong Kong Government, and the Scientific Committee on Vaccine Preventable Diseases of the Hong Kong Government; and is an Associated Editor for the journals Vaccine and Diagnostics. MHC, ART, and WMC declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.) |
| تواريخ الأحداث: | Date Created: 20240718 Latest Revision: 20240718 |
| رمز التحديث: | 20240719 |
| DOI: | 10.1016/S1473-3099(24)00353-0 |
| PMID: | 39025098 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1474-4457 |
|---|---|
| DOI: | 10.1016/S1473-3099(24)00353-0 |