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

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Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study
Age and Ageing ( IF 6.0 ) Pub Date : 2024-08-14 , DOI: 10.1093/ageing/afae180
Francisco Tsz Tsun Lai _{1,

2,

3} , Boyuan Wang ₂ , Cuiling Wei ₁ , Celine Sze Ling Chui _{3,

4,

5,

6} , Xue Li _{1,

3,

7} , Ching Lung Cheung _{1,

3} , Ian Chi Kei Wong _{1,

3,

8,

9,

10} , Esther Wai Yin Chan _{1,

3} , Eric Yuk Fai Wan _{1,

2,

3,

6}

Affiliation

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Southern District, 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, 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region, China.
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.
School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region, China.
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Southern District, Hong Kong Special Administrative Region, China.
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.
Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 102 Pok Fu Lam Road, Southern District, Hong Kong Special Administrative Region, China.
Aston Pharmacy School, Aston University, Birmingham, B4 7ET, United Kingdom.
Department of Pharmacy, The University of Hong Kong-Shenzhen Hospital, 1 Haiyuan First Road, Futian District, Shenzhen, China.
School of Pharmacy, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

Background 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. Methods 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. Results 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. Conclusions Molnupiravir and nirmatrelvir-ritonavir are moderately effective in reducing mortality risk among hospitalised oldest-old patients with COVID-19, regardless of their vaccination status.

更新日期：2024-08-14

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