Is Azvudine Comparable to Nirmatrelvir-Ritonavir in Real-World Efficacy and Safety for Hospitalized Patients with COVID-19? A Retrospective Cohort Study

Abstract

Introduction Azvudine and nirmatrelvir-ritonavir are more extensively used to treat COVID-19 in China due to their earlier approval by the National Medical Products Administration. However, there has been a scarcity of research directly comparing the clinical outcomes between azvudine and nirmatrelvir-ritonavir till now. We aimed to make a head-to-head comparison of the efficacy and safety of azvudine or nirmatrelvir-ritonavir in hospitalized patients with COVID-19 in China. Methods This retrospective cohort study was conducted using data collected from Tongde Hospital of Zhejiang Province between December 2022 and January 2023. All-cause mortality, risk of progressing to a critical condition, proportion with nucleic-acid negative conversion ( P NANC ), time to first nucleic-acid negative conversion ( T FNANC ), length of hospital stay and incidence of adverse events were systematically assessed as outcomes. Multi-model regression analysis, propensity-score-matching analysis, subgroup analysis and several sensitivity analyses were applied to compare these outcomes. Results This study included a total of 1571 hospitalized patients with COVID-19, among whom 272 received nirmatrelvir-ritonavir and 156 received azvudine. We found no significant differences in all-cause mortality (HR 1.41; 95% CI 0.56–3.56; P = 0.471), risk of progressing to critical COVID-19 (HR 1.67; 95% CI 0.78–3.60; P = 0.189), P NANC (HR 0.87; 95% CI 0.69–1.09; P = 0.220), length of stay ( β − 0.82; 95% CI − 2.78 to 1.15; P = 0.414) and adverse event rate (3.21% vs. 4.41%, P = 0.538) between the two groups, although azvudine was slightly less effective than nirmatrelvir-ritonavir. Meanwhile, the azvudine group exhibited a significantly longer T FNANC ( β 2.53; 95% CI 0.76–4.29; P = 0.005) than the nirmatrelvir-ritonavir group. Results were similar for propensity-score matching and multiple sensitivity analyses. Conclusion Azvudine probably possessed comparable efficacy and safety to nirmatrelvir-ritonavir, although it was less effective than nirmatrelvir-ritonavir for some outcomes. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00845-7.

Comparison of Azvudine and Nirmatrelvir/Ritonavir and Combined Use in Patients with COVID-19

“…Similar to Gao et al, 11 the confounding factors in the laboratory test results was balanced in our study to ensure the greatest possible reliability of the findings. Consistent with our study's results, studies by Zhao Q et al 32 and Zhao X et al 33 also found that there was no significant difference in overall mortality between the nirmatrelvir/ritonavir and azvudine groups. However, Dian et al 12 found that among patients with COVID-19 and comorbidities, the risk of composite disease progression was lower in the azvudine group than in the nirmatrelvir/ ritonavir group.…”

Efficacy and safety of azvudine in symptomatic adult COVID-19 participants who are at increased risk of progressing to critical illness: a study protocol for a multicentre randomized double-blind placebo-controlled phase III trial

“…However, inconsistent results are found among different studies regarding the impact of azvudine on all-cause mortality [ 17 , 37 – 39 ]. Nonetheless, there are promising results showing that there was no difference in mortality between COVID-19 patients using Paxlovid and those using azvudine, which was a consistent finding in two retrospective cohort studies [ 40 , 41 ].…”

Effectiveness and safety of azvudine in COVID-19: A systematic review and meta-analysis

“…The pooled estimate of nine studies [ 19 , 20 , 27 – 29 , 32 , 33 , 37 , 38 ] showed a significant difference in mortality rate between patients receiving azvudine and SOC (RR = 0.48, 95% CI: 0.40 to 0.57, P < 0.001, I 2 = 0%, GRADE certainty: moderate) ( Fig 2 ). According to the pooled estimate, seven studies [ 6 , 7 , 25 , 32 , 35 – 37 ] revealed a significant difference in mortality rate between the azvudine and nirmatrelvir-ritonavir groups (RR = 0.73, 95% CI: 0.58 to 0.92, P < 0.05, I 2 = 41%, GRADE certainty: moderate) ( Fig 3 ).…”

“…The pooled estimate of four papers [ 8 , 13 , 27 , 30 ], showed a significant difference in negative PCR conversion time between the azvudine and SOC/PBO groups (SMD = - 0.75, 95% CI: -1.29, - 0.21; P < 0.05, I 2 = 75%, GRADE certainty: low) ( Fig 4 ). The pooled estimate of three papers [ 14 , 35 , 36 ] highlighted no significant differences between the azvudine and nirmatrelvir-ritonavir groups concerning negative PCR conversion time (SMD = 2.14, 95% CI: -1.08, 5.36; P = 0.19, I 2 = 99%, GRADE certainty: low) ( Fig 5 ).…”

“…The pooled estimates of four papers [ 8 , 13 , 37 , 38 ] with 1801 patients indicated that the azvudine and SOC/PBO groups were not significantly different in length of hospital stay (SMD = - 1.34, 95% CI: -2.68, 0.005; P = 0.05, I 2 = 99%, GRADE certainty: low) ( Fig 6 ). According to the pooled estimate of three papers, [ 35 – 37 ] the azvudine and nirmatrelvir-ritonavir groups were not significantly different regarding length of hospital stay (SMD = - 0.49, 95% CI: -1.52, 0.52; P = 0.34, I 2 = 98%, GRADE certainty: low) ( Fig 7 ).…”