Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment.
Resistance. Variants may be resistant to paxlovid1-3. Use may promote the emergence of variants that weaken host immunity and potentially contribute to long COVID4. Confounding by contraindication. Hoertel et al. find that over 50% of patients that died had a contraindication for the use of Paxlovid5. Retrospective studies that do not exclude contraindicated patients may significantly overestimate efficacy. Black box warning. The FDA notes that "severe, life-threatening, and/or fatal adverse reactions due to drug interactions have been reported in patients treated with paxlovid"6. AKI.Kamo et al. show significantly increased risk of acute kidney injury.
{ 'indexed': {'date-parts': [[2024, 8, 15]], 'date-time': '2024-08-15T00:19:03Z', 'timestamp': 1723681143148},
'reference-count': 27,
'publisher': 'Oxford University Press (OUP)',
'issue': '8',
'license': [ { 'start': { 'date-parts': [[2024, 8, 1]],
'date-time': '2024-08-01T00:00:00Z',
'timestamp': 1722470400000},
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{'name': 'Government of the Hong Kong Special Administrative Region'},
{'name': 'Research Grants Council'}, {'name': 'Collaborative Research Fund'},
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'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\xa0years), 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>',
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'is-referenced-by-count': 0,
'title': 'Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a '
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Late treatment is less effective
lai2
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