A large-scale study reveals comparable efficacy of azvudine to Paxlovid, fewer side effects and potential anticancer benefits in liver cancer patients.
Study: Actual efficacy and safety of oral azvudine versus nirmatrelvir-ritonavir (Paxlovid) in hospitalized patients with COVID-19: a multicenter, retrospective, cohort study. Image credit: Cryptographer/Shutterstock.com
In a recent study published in Signal Transduction and Targeted Therapya group of investigators compared the efficacy and safety of azvudine versus nirmatrelvir-ritonavir (Paxlovid) in hospitalized patients with coronavirus disease 2019 (COVID-19), focusing on clinical outcomes, adverse events (AEs), and potential benefits for patients with malignant tumors.
Background
Since the December 2019 outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it has led to more than 776 million infections and 7 million deaths worldwide as of August 2024. Despite vaccination reducing severe cases, its effectiveness against immune-preventing variants remains limited.
Treatment for COVID-19 mainly includes antiviral and immunomodulatory drugs, but the latter are effective mainly in severe cases. Paxlovid and azvudine are widely used antivirals, but their comparative efficacy and safety remain under debate.
Further research is needed to clarify their role in the management of COVID-19 and related conditions such as hepatocellular carcinoma.
About the study
The present multicenter, retrospective cohort study was conducted in Henan and Xinjiang provinces of China, involving hospitalized patients with confirmed SARS-CoV-2 infection between December 5, 2022 and January 31, 2023.
The study population included 37,606 patients from ten hospitals in Henan and 3,270 patients from one hospital in Xinjiang. Eligibility criteria required participants to be 18 years of age or older, have a positive reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2, and have received standard therapy along with azvudine or Paxlovid.
Patients who did not receive antiviral agents, received other antiviral regimens, were pregnant, or had contraindications to either drug were excluded. Data were collected from electronic medical records, including demographics, admissions, outcomes, prescriptions, and laboratory results.
Participants were grouped by medication prescription and 1:2 propensity score matching (PSM) ensured balance on key covariates. Outcomes included all-cause death, disease progression, and AEs, categorized according to the Common Terminology Criteria for Adverse Events Version 5.0.
Statistical analyzes used Kaplan-Meier curves, Cox regression, and subgroup assessments. Sensitivity analyzes addressed missing values, alternative models, and premature dropout or mortality. The study adhered to the ethical guidelines based on the Declaration of Helsinki.
Study results
The study included 7,145 patients with confirmed COVID-19 from ten hospitals in Henan Province, China. After strict inclusion and exclusion criteria, 6,943 patients receiving azvudine and 1,202 receiving paxlovid were eligible for analysis. PSM in a 2:1 ratio balanced the baseline characteristic, yielding 2,404 azvudine and 1,202 Paxlovid recipients for the final cohort.
The primary outcome was all-cause death, with 469 deaths observed: 288 in the azvudine group and 181 in the paxlovid group. Kaplan–Meier analysis showed a significantly lower risk of death in the azvudine group compared to Paxlovid (p = 0.038).
Multivariable Cox regression analysis confirmed this, with a hazard ratio (HR) of 0.82 (95% confidence interval [CI]: 0.676-0.987, p = 0.036). Complex disease progression occurred in 681 patients: 446 in the azvudine group and 235 in the Paxlovid group.
Kaplan-Meier analysis revealed no significant difference between groups (p = 0.95) and Cox analysis gave an HR of 1.15 (95% CI: 0.975-1.345, p = 0.097).
Sensitivity analyzes supported the validity of these findings. Results were consistent across multiple methods of handling missing data, alternative imputation models, and exclusion of early dropouts or deaths.
For example, after imputing missing values, Cox analysis showed a 21% lower risk of death with azvudine (HR: 0.79, 95% CI: 0.658–0.959, p = 0.016). A probit-based matching model also showed a significant mortality risk reduction for azvudine compared to Paxlovid (HR: 0.73, 95% CI: 0.603-0.884, p = 0.001).
Validation in a cohort from Xinjiang province, including 79 azvudine and 78 Paxlovid recipients, showed no significant differences in composite outcomes (p = 0.27). However, Cox analysis revealed a lower mortality risk for azvudine (HR: 0.53, 95% CI: 0.283-0.989, p = 0.046).
Subgroup analyzes showed that azvudine was particularly beneficial for patients starting treatment more than five days after diagnosis (HR: 0.56, 95% CI: 0.39-0.78) and for those with primary malignancies (HR : 0.33, 95% CI: 0.20–0.54).
Safety assessments showed fewer AEs with azvudine compared to Paxlovid, particularly for grade 1 and 2 AEs. These findings suggest that azvudine may be a safer and more effective alternative to Paxlovid for some patients hospitalized with COVID-19.
conclusions
In summary, this large-scale, multicenter, retrospective cohort study highlighted the efficacy and safety of azvudine compared with Paxlovid in hospitalized patients with COVID-19. Among 37,606 patients analyzed, those receiving azvudine had a lower risk of all-cause death and comparable rates of complex disease progression compared with Paxlovid.
Subgroup analyzes revealed the greatest benefits of azvudine for patients with malignancies, moderate disease, or delayed treatment initiation.
In addition, azvudine demonstrated significant antitumor effects, suppressing the proliferation of hepatocellular carcinoma cells and enhancing immune responses.
