Real‐world effectiveness of Azvudine versus nirmatrelvir–ritonavir in hospitalized patients with COVID‐19: A retrospective cohort study

Abstract

Chinese guidelines prioritize the use of Azvudine and nirmatrelvir-ritonavir in COVID-19 patients. Nevertheless, the real-world effectiveness of Azvudine versus nirmatrelvir-ritonavir is still lacking, despite clinical trials showing their effectiveness compared with matched controls. To compare the effectiveness of Azvudine versus nirmatrelvir-ritonavir treatments in real-world clinical practice, we identified 2118 hospitalized COVID-19 patients, with a follow-up of up to 38 days. After exclusions and propensity score matching, we included 281 Azvudine recipients and 281 nirmatrelvir-ritonavir recipients who did not receive oxygen therapy at admission. The lower crude incidence rate of composite disease progression outcome (7.83 vs. 14.83 per 1000 person-days, p = 0.026) and all-cause death (2.05 vs. 5.78 per 1000 person-days, p = 0.052) were observed among Azvudine recipients. Azvudine was associated with lower risks of composite disease progression outcome (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.32-0.94) and all-cause death (HR: 0.40; 95% CI: 0.16-1.04). In subgroup analyses, the results of composite outcome retained significance among patients aged <65 years, those having a history of disease, those with severe COVID-19 at admission, and those receiving antibiotics.

Evaluate clinical effectiveness of Azvudine with data rather than speculation

“…7 As our study mainly included severe COVID-19 patients in China, the limited efficacy of nirmatrelvir-ritonavir is not surprising. 3,8 While Ma et al found a faster time to nucleic acid negative conversion in patients receiving nirmatrelvir-ritonavir compared to those receiving Azvudine, 1 it did not entirely negate our findings that support the better clinical benefit of Azvudine. 3 Evaluating a drug's effectiveness requires clinical data, rather than piecing together several basic articles to make a speculation solely based on its antiviral effect.…”

“…3,8 While Ma et al found a faster time to nucleic acid negative conversion in patients receiving nirmatrelvir-ritonavir compared to those receiving Azvudine, 1 it did not entirely negate our findings that support the better clinical benefit of Azvudine. 3 Evaluating a drug's effectiveness requires clinical data, rather than piecing together several basic articles to make a speculation solely based on its antiviral effect. For instance, remdesivir can effectively inhibit COVID-19 infection in vitro but has no significant effect on COVID-19 patients who are already being ventilated.…”

“…Nevertheless, it was not necessary for our study, which aimed to evaluate the real-world clinical effectiveness (composite outcomes and mortality). 3 Azvudine and nirmatrelvir-ritonavir were recommended for the treatment of COVID-19 patients as early as possible, but these drugs were not strictly used according to the instructions during the special period. We acknowledged several limitations in our retrospective study, including the possibility of selection bias and confounding by indication.…”

“…We also emphasized that our conclusions were solely based on data from our hospital and that the generalization of our findings required more high-quality and multi-center clinical trials. 3 As clinicians, with limited knowledge about drug experimental and pharmacokinetics studies, we refrain from making any response on the topic of its antiviral effect. If there are any questions concerning the antiviral effect, we suggest contacting the corresponding authors of these studies.…”

Azvudine and nirmatrelvir–ritonavir in hospitalized patients with moderate‐to‐severe COVID‐19: Emulation of a randomized target trial

“…In regions with limited healthcare resources, patients may be unable to access antiviral agents within 5 days of onset and hospitals are admitting more severe patients. In December 2022, only 9.4%–18.2% of patients with COVID‐19 who were admitted to hospitals were accessible antiviral drugs within 5 days after onset in China 16 . It remains unclear whether patients admitted to hospitals after 5‐day onset, who are typically severe cases, still benefit from antiviral agents.…”