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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

Choi et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0
Jul 2024  
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Mortality 34% Improvement Relative Risk ICU admission 37% Ventilatory support 45% Paxlovid for COVID-19  Choi et al.  EARLY TREATMENT Is early treatment with paxlovid beneficial for COVID-19? Retrospective 4,540 patients in China (March - December 2022) Lower mortality (p=0.0064) and lower oxygen therapy (p=0.029) c19early.org Choi et al., The Lancet Infectious Dis.., Jul 2024 Favorspaxlovid Favorscontrol 0 0.5 1 1.5 2+
Target trial emulation study of 18,196 hospitalized COVID-19 patients in Hong Kong showing significantly higher ICU admission and AKI with remdesivir + paxlovid compared with paxlovid alone, and lower mortality and ventilatory support with remdesivir + paxlovid compared with remdesivir alone. Patients were treated within 5 days of diagnosis, however the time from onset is not known.
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.
Study covers remdesivir and paxlovid.
risk of death, 34.0% lower, HR 0.66, p = 0.006, treatment 308, control 4,232, remdesivir+paxlovid vs. remdesivir, day 90.
risk of ICU admission, 37.0% lower, HR 0.63, p = 0.26, treatment 308, control 4,232, remdesivir+paxlovid vs. remdesivir, day 90.
ventilatory support, 45.0% lower, HR 0.55, p = 0.03, treatment 308, control 4,232, remdesivir+paxlovid vs. remdesivir, day 90.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Choi et al., 15 Jul 2024, retrospective, China, peer-reviewed, mean age 74.0, 8 authors, study period 16 March, 2022 - 31 December, 2022. Contact: ivanhung@hku.hk.
This PaperPaxlovidAll
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
Ming Hong Choi, Eric Yuk Fai Wan, Ian Chi Kei Wong, Esther Wai Yin Chan, Wing Ming Chu, Anthony Raymond Tam, Kwok Yung Yuen, Ivan Fan Ngai Hung
The Lancet Infectious Diseases, doi:10.1016/s1473-3099(24)00353-0
Background Remdesivir (Veklury, Gilead Sciences, Foster
References
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