Nirmatrelvir, molnupiravir effective against Omicron in high-risk patients

Treatment with either nirmatrelvir or molnupiravir helps reduce mortality and hospitalization in COVID-19 patients infected with the Omicron variant and are at high-risk of progressing to severe disease, as shown in a study.

Data from 68,867 patients (42.7 percent aged ≥65 years, 38.9 percent men, 74.7 percent non-Hispanic White) from the Cleveland Clinic Health System in US showed that compared with no treatment, nirmatrelvir lowered the risk of death by 84 percent (hazard ratio [HR], 0.16, 95 percent confidence interval [CI], 0.11–0.23) while molnupiravir did so by 77 percent (HR, 0.23, 95 percent CI, 0.16–0.34). [JAMA Netw Open  2023;6:e2335077]

In addition, patients who received either nirmatrelvir or molnupiravir were 37 percent and 41 percent less likely to be hospitalized (composite endpoint of hospitalization or death: HR, 0.63, 95 percent CI, 0.59–0.68 and HR, 0.59, 95 percent CI, 0.53–0.66), respectively.

The protective benefit of the two antiviral medications against both death and hospitalization was seen across subgroups defined by age, race and ethnicity, date of COVID-19 diagnosis, vaccination status, previous infection status, and coexisting medical conditions.

“Our findings are consistent with those of the phase III clinical trials. However, the clinical trials were conducted among unvaccinated populations with limited natural immunity in the Delta era, whereas our study was conducted in a population including vaccinated and previously infected patients during the more recent Omicron period,” characterized by the currently circulating BQ.1.1 and XBB.1.5 strains, according to the investigators. [N Engl J Med 2022;386:509-520; N Engl J Med 2022;386:1397-1408]

“With a very large sample size, we were able to obtain precise estimates for the association of both drugs with hospitalization and death, not only for the whole population but also for important subgroups,” they added.

Preferred antiviral

The US National Institutes of Health COVID-19 treatment guidelines recommend nirmatrelvir as the first-choice treatment for patients at high risk of progressing to severe COVID-19. Molnupiravir is an alternative treatment that should be used only in cases where nirmatrelvir is not available, cannot be used, or is not medically appropriate. [https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf]

The preference for nirmatrelvir over molnupiravir was based on the results of trials wherein the reduction in the risk of progression to severe COVID-19 was lower with nirmatrelvir vs placebo (89 percent) than with molnupiravir vs placebo (48 percent). However, there were limited data on mortality, with only one death recorded in the molnupiravir group vs nine in the placebo group through day 29, and with no deaths in the nirmatrelvir group vs seven in the placebo group through day 28. [N Engl J Med 2022;386:509-520; N Engl J Med 2022;386:1397-1408]

“Our study, which had more patients and longer follow-up, demonstrated that both nirmatrelvir and molnupiravir were associated with reductions in mortality. This finding is particularly important because nirmatrelvir has substantial drug-drug interactions with concomitant medications,” the investigators pointed out.

Overall, the data presented in the study suggest that both antiviral drugs can be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19, they said.

Study details

Of the patients included in the study, 22,594 received nirmatrelvir and 5,311 received molnupiravir. Most COVID-19 cases were diagnosed between 22 June 2022 and 20 February 2023, during which BA.4/BA.5, BQ.1/BQ.1.1, and XBB/XBB.1.5 were circulating.

Those who received nirmatrelvir (mean age 61.8 years, 82 percent non-Hispanic White) had a booster vaccination rate of 75 percent and mean socioeconomic index of 0.30, whereas the patients who were eligible for nirmatrelvir but received no treatment (mean age 54.0 years, 69 percent non-Hispanic White) had a booster vaccination rate of 50 percent and mean socioeconomic index of 0.33. Similar differences were observed between the patients who received molnupiravir and those who were eligible for molnupiravir but received no treatment.

By the end of the study, 645 patients had died, including 30 in the nirmatrelvir group, 27 in the molnupiravir group, and 588 in the no-treatment comparison groups. A total of 5,368 patients had been hospitalized.