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Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study

Lai et al., Age and Ageing, doi:10.1093/ageing/afae180
Aug 2024  
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Mortality 10% Improvement Relative Risk Molnupiravir for COVID-19  Lai et al.  LATE TREATMENT Is late treatment with molnupiravir beneficial for COVID-19? Retrospective 13,642 patients in China Lower mortality with molnupiravir (p=0.0068) c19early.org Lai et al., Age and Ageing, August 2024 Favorsmolnupiravir Favorscontrol 0 0.5 1 1.5 2+
Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-14. Multiple analyses have identified variants potentially created by molnupiravir15-19.
Standard of Care (SOC): SOC for COVID-19 in the study country, China, is average with moderate average efficacy for approved treatments20.
Study covers molnupiravir and paxlovid.
risk of death, 10.5% lower, HR 0.90, p = 0.007, treatment 4,975, control 8,667, day 28.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lai et al., 14 Aug 2024, retrospective, China, peer-reviewed, 9 authors.
This PaperMolnupiravirAll
DOI record: { "DOI": "10.1093/ageing/afae180", "ISSN": [ "0002-0729", "1468-2834" ], "URL": "http://dx.doi.org/10.1093/ageing/afae180", "abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Molnupiravir and nirmatrelvir-ritonavir are orally administered pharmacotherapies for mild to moderate COVID-19. However, the effectiveness of these drugs among very old (≥80 years), hospitalised patients remains unclear, limiting the risk–benefit assessment of these antivirals in this specific group. This study investigates the effectiveness of these antivirals in reducing mortality among this group of hospitalised patients with COVID-19.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>Using a territory-wide public healthcare database in Hong Kong, a target trial emulation study was conducted with data from 13 642 eligible participants for the molnupiravir trial and 9553 for the nirmatrelvir-ritonavir trial. The primary outcome was all-cause mortality. Immortal time and confounding bias was minimised using cloning-censoring-weighting approach. Mortality odds ratios were estimated by pooled logistic regression after adjusting confounding biases by stabilised inverse probability weights.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>Both molnupiravir (HR: 0.895, 95% CI: 0.826–0.970) and nirmatrelvir-ritonavir (HR: 0.804, 95% CI: 0.678–0.955) demonstrated moderate mortality risk reduction among oldest-old hospitalised patients. No significant interaction was observed between oral antiviral treatment and vaccination status. The 28-day risk of mortality was lower in initiators than non-initiators for both molnupiravir (risk difference: −1.09%, 95% CI: −2.29, 0.11) and nirmatrelvir-ritonavir (risk difference: −1.71%, 95% CI: −3.30, −0.16) trials. The effectiveness of these medications was observed regardless of the patients’ prior vaccination status.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>Molnupiravir and nirmatrelvir-ritonavir are moderately effective in reducing mortality risk among hospitalised oldest-old patients with COVID-19, regardless of their vaccination status.</jats:p>\n </jats:sec>", "author": [ { "ORCID": "http://orcid.org/0000-0002-9121-1959", "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Department of Family Medicine and Primary Care , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" } ], "authenticated-orcid": false, "family": "Lai", "given": "Francisco Tsz Tsun", "sequence": "first" }, { "affiliation": [ { "name": "Department of Family Medicine and Primary Care , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" } ], "family": "Wang", "given": "Boyuan", "sequence": "additional" }, { "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" } ], "family": "Wei", "given": "Cuiling", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-1513-8726", "affiliation": [ { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" }, { "name": "School of Nursing , Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "School of Public Health , Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Advanced Data Analytics for Medical Science (ADAMS) Limited , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" } ], "authenticated-orcid": false, "family": "Chui", "given": "Celine Sze Ling", "sequence": "additional" }, { "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" }, { "name": "Department of Medicine , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 102 Pok Fu Lam Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 102 Pok Fu Lam Road, Southern District, Hong Kong Special Administrative Region , China" } ], "family": "Li", "given": "Xue", "sequence": "additional" }, { "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" } ], "family": "Cheung", "given": "Ching Lung", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-8242-0014", "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" }, { "name": "Aston Pharmacy School, Aston University , Birmingham, B4 7ET , United Kingdom" }, { "name": "Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital , 1 Haiyuan First Road, Futian District, Shenzhen , China" }, { "name": "School of Pharmacy, Macau University of Science and Technology , Avenida Wai Long, Taipa, Macau , China" } ], "authenticated-orcid": false, "family": "Wong", "given": "Ian Chi Kei", "sequence": "additional" }, { "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" } ], "family": "Chan", "given": "Esther Wai Yin", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6275-1147", "affiliation": [ { "name": "Centre for Safe Medication Practice and Research , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Department of Family Medicine and Primary Care , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "The University of Hong Kong , School of Clinical Medicine, Li Ka Shing Faculty of Medicine, , 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region , China" }, { "name": "Laboratory of Data Discovery for Health (D24H) , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" }, { "name": "Advanced Data Analytics for Medical Science (ADAMS) Limited , 19 Science Park West Avenue, Hong Kong Science Park, Tai Po District, Hong Kong Special Administrative Region , China" } ], "authenticated-orcid": false, "family": "Wan", "given": "Eric Yuk Fai", "sequence": "additional" } ], "container-title": "Age and Ageing", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2024, 8, 14 ] ], 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"source": "Crossref", "subject": [], "subtitle": [], "title": "Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study", "type": "journal-article", "volume": "53" }
Late treatment
is less effective
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