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Clin Ther . Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence Fr

tetano

Editor, Senior Moderator
Clin Ther


. 2025 Jul 3:S0149-2918(25)00214-0.
doi: 10.1016/j.clinthera.2025.06.008. Online ahead of print. Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant

Yi Zhang[SUP] 1 [/SUP], Yuezhen Zhu[SUP] 1 [/SUP], Hui Yang[SUP] 1 [/SUP], Chunguo Jiang[SUP] 2 [/SUP], Wanying Chen[SUP] 1 [/SUP], Hui Zhang[SUP] 3 [/SUP], Xintong Zhang[SUP] 1 [/SUP], Han Wu[SUP] 1 [/SUP], Jia Li[SUP] 1 [/SUP], Zhuoling An[SUP] 4 [/SUP]



Affiliations
Abstract

Purpose: The rapid spread of the coronavirus-2019 (COVID-19) Omicron EG.5 variant poses challenges to existing treatment strategies, and comparative real-world evidence between simnotrelvir-ritonavir and nirmatrelvir-ritonavir remains limited.
Methods: We conducted a single-center retrospective study from July 01 to December 31, 2023, involving outpatient-diagnosed COVID-19 patients. We performed a descriptive analysis of epidemiologic characteristics, followed by regression analysis to identify key factors. Efficacy and safety differences between simnotrelvir-ritonavir and nirmatrelvir-ritonavir were then compared.
Findings: A total of 545 patients were included, with 93.21% presenting with general symptoms, 88.81% with respiratory symptoms, 10.28% with gastrointestinal symptoms, and 9.36% with cardiovascular symptoms. Factors associated with delayed recovery included a BMI over 25 kg/m[SUP]2[/SUP] (P = 0.004), and symptoms lasting more than 3 days at presentation (P = 0.004). The efficacy of simnotrelvir-ritonavir and nirmatrelvir-ritonavir was comparable, with mean days to symptom recovery of 5.11 and 4.22 days, respectively. However, simnotrelvir-ritonavir had a higher incidence of adverse events (20.59%) compared to nirmatrelvir-ritonavir (6.69%), primarily gastrointestinal disorders.
Implications: During the Omicron EG.5 epidemic, general and respiratory symptoms predominated, with delayed recovery associated with being overweight, late treatment initiation, and multiple comorbidities. Simnotrelvir-ritonavir and nirmatrelvir-ritonavir demonstrated comparable efficacy, while simnotrelvir-ritonavir had a poorer safety profile.

Keywords: COVID-19; Nirmatrelvir-ritonavir; Omicron EG.5; Retrospective cohort study; Simnotrelvir-ritonavir.

 
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