TY - JOUR
T1 - Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Hospitalized Patients With COVID-19: A Target Trial Emulation Study
AU - Wan, Eric Yuk Fai
AU - Yan, Vincent Ka Chun
AU - Mok, Anna Hoi Ying
AU - Wang, Boyuan
AU - Xu, Wanchun
AU - Cheng, Franco Wing Tak
AU - Lai, Francisco Tsz Tsun
AU - Chui, Celine Sze Ling
AU - Li, Xue
AU - Wong, Carlos King Ho
AU - Li, Philip Hei
AU - Cowling, Benjamin John
AU - Hung, Ivan Fan Ngai
AU - Lau, Chak Sing
AU - Wong, Ian Chi Kei
AU - Chan, Esther Wai Yin
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85152621358&partnerID=8YFLogxK
UR - https://www.acpjournals.org/doi/10.7326/M22-3057
U2 - 10.7326/L23-0265
DO - 10.7326/L23-0265
M3 - Article
C2 - 36913693
AN - SCOPUS:85152621358
SN - 0003-4819
VL - 176
SP - 505
EP - 514
JO - Annals of Internal Medicine
JF - Annals of Internal Medicine
IS - 4
ER -