Effectiveness of Molnupiravir and Nirmatrelvir-Ritonavir in Hospitalized Patients With COVID-19 : A Target Trial Emulation Study.

Autor:	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, Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, and Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (E.Y.F.W., C.K.H.W.)., Yan VKC; 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, China (V.K.C.Y., F.W.T.C.)., Mok AHY; Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (A.H.Y.M., B.W., W.X.)., Wang B; Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (A.H.Y.M., B.W., W.X.)., Xu W; Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (A.H.Y.M., B.W., W.X.)., Cheng FWT; 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, China (V.K.C.Y., F.W.T.C.)., Lai FTT; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China (F.T.T.L.)., Chui CSL; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (C.S.L.C.)., Li X; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, and Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (X.L.)., Wong CKH; Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, and Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (E.Y.F.W., C.K.H.W.)., Li PH; Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (P.H.L., I.F.N.H., C.S.L.)., Cowling BJ; Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, and WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (B.J.C.)., Hung IFN; Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (P.H.L., I.F.N.H., C.S.L.)., Lau CS; Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China (P.H.L., I.F.N.H., C.S.L.)., 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, and Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China, Research Department of Practice and Policy, School of Pharmacy, University College London, London, United Kingdom, and Aston Pharmacy School, Aston University, Birmingham, United Kingdom (I.C.K.W.)., 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, and Laboratory of Data Discovery for Health (D24H), Hong Kong Science and Technology Park, Hong Kong, China, and Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, and The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, China (E.W.Y.C.).
Jazyk:	angličtina
Zdroj:	Annals of internal medicine [Ann Intern Med] 2023 Apr; Vol. 176 (4), pp. 505-514. Date of Electronic Publication: 2023 Mar 14.
DOI:	10.7326/M22-3057
Abstrakt:	Background: Whether hospitalized patients benefit from COVID-19 oral antivirals is uncertain. Objective: To examine the real-world effectiveness of molnupiravir and nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the Omicron outbreak. Design: Target trial emulation study. Setting: Electronic health databases in Hong Kong. Participants: The molnupiravir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 26 February and 18 July 2022 ( n = 16 495). The nirmatrelvir-ritonavir emulated trial included hospitalized patients with COVID-19 aged 18 years or older between 16 March and 18 July 2022 ( n = 7119). Intervention: Initiation of molnupiravir or nirmatrelvir-ritonavir within 5 days of hospitalization with COVID-19 versus no initiation of molnupiravir or nirmatrelvir-ritonavir. Measurements: Effectiveness against all-cause mortality, intensive care unit (ICU) admission, or use of ventilatory support within 28 days. Results: The use of oral antivirals in hospitalized patients with COVID-19 was associated with a lower risk for all-cause mortality (molnupiravir: hazard ratio [HR], 0.87 [95% CI, 0.81 to 0.93]; nirmatrelvir-ritonavir: HR, 0.77 [CI, 0.66 to 0.90]) but no significant risk reduction in terms of ICU admission (molnupiravir: HR, 1.02 [CI, 0.76 to 1.36]; nirmatrelvir-ritonavir: HR, 1.08 [CI, 0.58 to 2.02]) or the need for ventilatory support (molnupiravir: HR, 1.07 [CI, 0.89 to 1.30]; nirmatrelvir-ritonavir: HR, 1.03 [CI, 0.70 to 1.52]). There was no significant interaction between drug treatment and the number of COVID-19 vaccine doses received, thereby supporting the effectiveness of oral antivirals regardless of vaccination status. No significant interaction between nirmatrelvir-ritonavir treatment and age, sex, or Charlson Comorbidity Index was observed, whereas molnupiravir tended to be more effective in older people. Limitation: The outcome of ICU admission or need for ventilatory support may not capture all severe COVID-19 cases; unmeasured confounders, such as obesity and health behaviors, may exist. Conclusion: Molnupiravir and nirmatrelvir-ritonavir reduced all-cause mortality in both vaccinated and unvaccinated hospitalized patients. No significant reduction in ICU admission or the need for ventilatory support was observed. Primary Funding Source: Health and Medical Research Fund Research on COVID-19, Government of the Hong Kong Special Administrative Region; Research Grants Council, Collaborative Research Fund; and Health Bureau, Government of the Hong Kong Special Administrative Region.
Databáze:	MEDLINE
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