Comparative Effectiveness of Remdesivir in Early COVID-19 Treatment

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Evaluating inpatient mortality for patients without supplemental oxygen at admission across different variants of concern periods with insights from Dr. Andre Kalil.

Remdesivir, drug cleared to treat Covid-19.

Image Credits: Unsplash

Remdesivir, drug cleared to treat Covid-19.

Image Credits: Unsplash

Remdesivir has proven beneficial for hospitalized COVID-19 patients needing supplemental oxygen and those breathing room air. This study extends these findings to those hospitalized without the need for oxygen at admission, demonstrating a reduction in mortality even amid different SARS-CoV-2 variants of concern (VOC).

Andre Kalil MD, MPH, FACP, FIDSA, FCCM explains, “Our study evaluated several different COVID-19 waves, accounting for different strains and their respective virulence, and this extensive analysis of prolonged periods of time including different VOC shows a consistent clinical antiviral effect of remdesivir across the dominant variant eras. These findings also provide further evidence of a lack of meaningful escape of VOC from remdesivir at the population level, aligning with in vitro studies.”

3 Key Takeaways

  1. The study suggests that it is unethical to conduct further randomized controlled trials that withhold remdesivir from the control groups.
  2. Remdesivir reduces mortality rates in hospitalized COVID-19 patients across different stages of the disease and against various SARS-CoV-2 VOCs.
  3. Remdesivir treatment was associated with a statistically significant decrease in mortality among patients.

Among the 121,336 eligible patients, 58,188 treated with remdesivir showed a mortality rate of 5.4% at 14 days and 8.0% at 28 days, compared to 7.3% and 9.8% respectively for the 17,574 untreated patients. Treatment with remdesivir was associated with a statistically significant decrease in in-hospital mortality compared to those not receiving remdesivir (14-day adjusted hazard ratio (aHR): 0.75, 95% confidence interval (CI): 0.68-0.83; 28-day aHR: 0.83, 0.76-0.90). This notable reduction in mortality was consistent across various periods with different VOCs.

“Remdesivir has demonstrated significant mortality reduction in large randomized controlled trials in patients hospitalized for COVID-19 who require supplemental oxygen as well as in patients not hospitalized but diagnosed with COVID-19 at risk for disease progression,” according to Kalil. “Thus, from the biological and clinical perspectives after needing oxygen support, it is not surprising that this same antiviral should work in patients after hospitalization before oxygen support.”

Using data from a comprehensive multicenter US hospital database (December 2020 to April 2022), investigators compared the in-hospital mortality rates of COVID-19 patients admitted without needing oxygen. Patients who received remdesivir were matched 1:1 with those who did not, using propensity score matching to ensure comparability. Mortality and hospice discharge rates at 14 and 28 days were analyzed using Cox proportional hazards models.

“Based on the established survival benefits of remdesivir in patients hospitalized for COVID-19, further clinical trials would not be ethical, that is, it would be unethical to have patients hospitalized for COVID-19 not receiving remdesivir in the control group,” states Kalil.

Overall, these results underscore the potential survival advantage of initiating remdesivir treatment at the time of admission, throughout the dominant variant phases of the ongoing pandemic. This study aligns with the well-established therapeutic principle that initiating antiviral treatment earlier enhances its efficacy.

Reference

Kalil A, Mozaffari E, Chandak A, et. al. Remdesivir is Associated with Reduced Mortality in Patients Hospitalized for COVID-19 not Requiring Supplemental Oxygen. Open Forum Infectious Diseases. Published April 16, 2024. Accessed April 23, 2024. https://doi.org/10.1093/ofid/ofae202

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