Effectiveness of molnupiravir vs nirmatrelvir-ritonavir in non-hospitalised and hospitalised patients with COVID-19: a target trial emulation study.
EClinicalMedicine
; 64: 102225, 2023 Oct.
Article
em En
| MEDLINE
| ID: mdl-37753272
ABSTRACT
Background:
Molnupiravir and nirmatrelvir-ritonavir have emerged as promising options for COVID-19 treatment, but direct comparisons of their effectiveness have been limited. This study aimed to compare the effectiveness of these two oral antiviral drugs in non-hospitalised and hospitalised patients with COVID-19.Methods:
In this target trial emulation study, we used data from a territory-wide electronic health records database on eligible patients aged ≥18 years infected with COVID-19 who were prescribed either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16 March 2022 and 31 December 2022 in the non-hospitalised and hospitalised settings in Hong Kong. A sequence trial approach and 11 propensity score matching was applied based on age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index, comorbidities, and drug use within past 90 days. Cox regression adjusted with patients' characteristics was used to compare the risk of effectiveness outcomes (all-cause mortality, intensive care unit (ICU) admission or ventilatory support and hospitalisation) between groups. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (<4; ≥4), and number of COVID-19 vaccine doses received (0-1; ≥2 doses).Findings:
A total of 63,522 non-hospitalised (nirmatrelvir-ritonavir 31,761; molnupiravir 31,761) and 11,784 hospitalised (nirmatrelvir-ritonavir 5892; molnupiravir 5892) patients were included. In non-hospitalised setting, 336 events of all-cause mortality (nirmatrelvir-ritonavir 71, 0.22%; molnupiravir 265, 0.83%), 162 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir 71, 0.22%; molnupiravir 91, 0.29%), and 4890 events of hospitalisation (nirmatrelvir-ritonavir 1853, 5.83%; molnupiravir 3037, 9.56%) were observed. Lower risks of all-cause mortality (absolute risk reduction (ARR) at 28 days 0.61%, 95% CI 0.50-0.72; HR 0.43, 95% CI 0.33-0.56) and hospital admission (ARR at 28 days 3.73%, 95% CI 3.31-4.14; HR 0.72, 95% CI 0.67-0.76) were observed in nirmatrelvir-ritonavir users compared to molnupiravir users. In hospitalised setting, 509 events of all-cause mortality (nirmatrelvir-ritonavir 176, 2.99%; molnupiravir 333, 5.65%), and 50 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir 26, 0.44%; molnupiravir 24, 0.41%) were observed. Risk of all-cause mortality was lower for nirmatrelvir-ritonavir users than for molnupiravir users (ARR at 28 days 2.66%, 95% CI 1.93-3.40; HR 0.59, 95% CI 0.49-0.71). In both settings, there was no difference in the risk of intensive care unit admission or ventilatory support between groups. The findings were consistent across all subgroup's analyses.Interpretation:
Our analyses suggest that nirmatrelvir-ritonavir was more effective than molnupiravir in reducing the risk of all-cause mortality in both non-hospitalised and hospitalised patients. When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option.Funding:
HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government; Collaborative Research Fund, University Grants Committee, the HKSAR Government; and Research Grant from the Food and Health Bureau, the HKSAR Government; the Laboratory of Data Discovery for Health (D24H) funded by the AIR@InnoHK administered by Innovation and Technology Commission.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
1_ASSA2030
/
4_TD
Problema de saúde:
1_sistemas_informacao_saude
/
4_covid_19
Idioma:
En
Revista:
EClinicalMedicine
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China