Paxlovid, Lagevrio reduce mortality risk in patients with COVID-19

Key takeaways:

• Paxlovid was linked to a lower 30-day risk for death vs. no treatment: 1.25 vs. 5.47 per 1,000 participants.
• Lagevrio was also linked to a lower 30-day risk for death: 3.14 vs. 13.56 per 1,000 participants.

As an outpatient treatment for COVID-19, the antivirals Paxlovid and Lagevrio were both associated with reduced mortality rates, but only Paxlovid was associated with a reduction in hospitalization, data show.

In December 2021, the FDA initially granted Paxlovid (nirmatrelvir-ritonavir, Pfizer) and Lagevrio (molnupiravir, Merck) emergency use authorization for people with symptomatic COVID-19 who are at high risk for progression to severe COVID-19, Kristina L. Bajema, MD, MSc, an assistant professor of medicine at Oregon Health & Science University, and colleagues wrote in Annals of Internal Medicine. In May, nirmatrelvir-ritonavir received full approval, making it the first oral antiviral approved by the FDA to treat COVID-19 in adults.

Previous research has associated nirmatrelvir to a significant reduction in the risk for long COVID and post-acute death in patients with at least one risk factor for severe illness. However, there is limited information regarding how effective oral antivirals are in preventing short- and long-term COVID-19-related outcomes, the researchers wrote.

“Effectiveness studies of nirmatrelvir-ritonavir and molnupiravir are needed because early clinical trials were conducted among unvaccinated participants before the emergence of the omicron variant and subsequent sublineages,” Bajema and colleagues wrote. “Randomized controlled trials did not directly compare efficacy of antiviral agents, nor did they evaluate outcomes beyond 29 days after symptomatic infection.”

Bajema and colleagues conducted three retrospective target trial emulation studies to evaluate the efficacy of nirmatrelvir-ritonavir and molnupiravir as outpatient treatments for COVID-19.

The researchers compared matched cohorts of nirmatrelvir-ritonavir vs. no treatment, molnupiravir vs. no treatment and nirmatrelvir-ritonavir vs. molnupiravir among nonhospitalized patients in the Veterans Health Administration who tested positive for SARS-CoV-2 from January 2022 through July 2022 and were at risk for developing severe COVID-19.

Trial one included 10,552 patients who received nirmatrelvir-ritonavir; trial two included 3,926 patients who received molnupiravir; and trial three included 10,232 patients who received nirmatrelvir-ritonavir and 2,817 who received molnupiravir. Of the patients, 18% were unvaccinated, 87% were men and the median age was 66 years.

Compared with matched untreated control patients, Bajema and colleagues reported that patients who received nirmatrelvir-ritonavir had a lower 30-day risk for death, at 1.25 vs. 5.47 per 1,000 participants (risk difference [RD] = 4.22; 95% CI, 5.45-3), as well as 30-day hospitalization, at 22.07 vs. 30.32 per 1,000 participants (RD = 8.25; 95% CI, 12.27-4.23). Among patients alive at day 31, the researchers also observed a reduction in 31- to 180-day incidence of death (HR = 0.66; 95% CI, 0.49-0.89) but not hospitalization.

Those treated with molnupiravir also had a lower 30-day risk for death compared with no treatment — 3.14 vs. 13.56 per 1,000 participants (RD = 10.42; 95% CI, 13.49-7.35) — and a lower 31- to 180-day risk for death (HR = 0.67; 95% CI, 0.48-0.95). However, there was no significant reduction in hospitalization, according to the researchers.

In addition, there was no significant difference in 30-day or 31- to 180-day risk for death or hospitalization between matched molnupiravir- or nirmatrelvir-treated patients.

Overall, both nirmatrelvir-ritonavir and molnupiravir were associated with a 77% reduced risk for death, and nirmatrelvir-ritonavir was associated with a 27% reduced risk for hospitalization.

“Nirmatrelvir-ritonavir seems to be an effective treatment for eligible persons with COVID-19 to reduce risk for short-term outcomes of severe COVID-19. The benefit of molnupiravir may be more limited,” Bajema and colleagues concluded. “Further studies are needed to clarify the long-term effectiveness of oral antivirals with regard to incident post–COVID-19 conditions.”