Azvudine beats Paxlovid in reducing Covid-19 deaths

Azvudine beats Paxlovid in reducing Covid-19 deaths

A large study shows comparable effectiveness of azvudine to paxlovid, fewer side effects and potential antitumor benefits in patients with liver cancer.

In a recently published study in theSignal transduction and targeted therapyA group of researchers compared the efficacy and safety of azvudine with nirmalatrelvir-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 outbreak of Covid-19 in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this has resulted in over 776 million infections and 7 million deaths as of August 2024. Despite vaccination that reduced serious cases, its effectiveness against immune-evasive variants remains limited.

COVID-19 treatment mainly includes antiviral and immunomodulatory drugs, but the latter mainly works in severe cases. Paxlovid and azvudine are widely used antivirals, but their comparative effectiveness and safety remain debated.

Further research is needed to clarify their role in the management of Covid-19 and associated conditions such as hepatocellular carcinoma.

About the study

The present multicenter, retrospective cohort study was conducted in Henan and Xinjiang provinces, 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. The participant criteria required participants to have received a positive reverse transcription polymerase chain reaction (Paxlovid) test for SARS-CoV-2 (RT-PCR) aged 18 years or older (AZVUDINE or PAXLOVID).

Patients who did not receive antiviral agents were receiving other antiviral therapy, were pregnant, or had contraindications to either drug ruled out. Data were collected from electronic medical records, including demographics, admissions, outcomes, prescriptions, and laboratory results.

Participants were grouped by drug prescription and propensity score (PSM) with a ratio of 1:2. Outcomes included overall control, disease progression, and AES, which were categorized according to the Common Terminology Criteria for Adverse Events version 5.0.

Statistical analyzes used Kaplan-Meier curves, Cox regression, and subgroup scores. Sensitivity analyzes addressed missing values, alternative models, and early discharge or mortality. The study adhered to ethical guidelines according to the Declaration of Helsinki.

Study results

The study included 7,145 patients with confirmed Covid-19 from ten hospitals in Henan Province, China. Following strict inclusion and exclusion criteria, 6,943 patients receiving azvudine and 1,202 receiving paxlovid were eligible for analysis. PSM at a 2:1 ratio balanced baseline characteristics, yielding 2,404 azvudine and 1,202 paxlovid recipients for the final cohort.

The primary outcome was death, with 469 deaths: 288 in the azvudine group and 181 in the paxlovid group. The 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). Disease progression occurred in 681 patients: 446 in the azvudine group and 235 in the paxlovid group.

Kaplan-Meier analysis showed no significant difference between groups (p = 0.95), and COX analysis gave a HR of 1.15 (95% CI: 0.975-1.345, p = 0.097).

Sensitivity analyzes supported the accuracy of these results. Results remained consistent across multiple methods of addressing missing data, alternative matching models, and exclusion of early discharges or deaths.

For example, after imputation of missing values, the COX analysis showed a 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 reduction in mortality risk for azvudine compared to paxlovid (HR: 0.73, 95% CI: 0.603-0.884, p = 0.001).

Validation in a cohort from Xinjiang province of 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 more than five days after diagnosis (HR: 0.56, 95% CI: 0.39-0.78) and patients with primary malignancies (HR: 0.33, 95% CI: 0.20-0.54).

Safety assessments showed fewer AEs with azvudine compared to paxlovid, particularly for Class 1 and 2 AEs. These results suggest that azvudine may be a safer and more effective alternative to paxlovid for certain hospitalized COVID-19 patients.

Conclusions

In conclusion, this large, multicenter, retrospective cohort study highlighted the efficacy and safety of azvudine compared to paxlovid in hospitalized COVID-19 patients. In 37,606 patients analyzed, those who received azvudine showed a lower risk of death and comparable rates of composite disease progression compared with paxlovid.

Subgroup analyzes revealed greater benefit of azvudine for patients with malignancies, moderate disease, or delayed treatment initiation.

In addition, azvudine showed significant antitumor effects, suppressed the proliferation of hepatocellular carcinoma cells and improved immune responses.

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