Two new studies describe the benefits of the antiviral drugs nirmatrelvir-ritonavir (Paxlovid) and molnupiravir in reducing SARS-CoV-2 Omicron hospitalizations and death, with one finding that the former is more effective than the latter at lowering death rates.
Paxlovid and molnupiravir are used to treat nonhospitalized COVID-19 patients at high risk for severe illness within 5 days after symptom onset.
Drugs offered comparable protection
In JAMA Network Open today, researchers from the University of North Carolina and Cleveland Clinic report on 68,867 outpatients diagnosed as having COVID-19 at Cleveland Clinic from April 2022 to February 2023. The observational study spanned the predominance of the Omicron subvariants BA.2, BA.4/BA.5, BQ.1/BQ.1.1, and XBB/XBB.1.5.
Of the 68,867 patients, 42.7% were aged 65 years or older, 38.9% were male, and 74.7% were White. Follow-up was 90 days.
The adjusted hazard ratio (HR) for hospitalization and death was 0.63 (95% confidence interval [CI], 0.59 to 0.68) for Paxlovid and 0.59 (95% CI, 0.53 to 0.66) for molnupiravir.
Thirty of 22,594 Paxlovid recipients (0.1%), 27 of 5,311 molnupiravir recipients (0.5%), and 588 of 40,962 untreated patients (1.4%) died within 90 days of infection. The cumulative incidence of death at 90 days after diagnosis was 0.15% (95% CI, 0.10% to 0.21%) for treated patients and 1.05% (95% CI, 0.95% to 1.15%) for untreated patients.
The adjusted HRs for death were 0.16 (95% CI, 0.11 to 0.23) for Paxlovid and 0.23 (95% CI, 0.16 to 0.34) for molnupiravir. The adjusted HRs for hospitalization or death were 0.63 (95% CI, 0.59 to 0.68) for Paxlovid and 0.59 (95% CI, 0.53 to 0.66) for molnupiravir.
Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19.
Among Paxlovid recipients aged 65 years or older, the cumulative incidence of death at 90 days was 0.25% (95% CI, 0.17% to 0.37%) for the treated and 2.42% (95% CI, 1.15% to 2.67%) for the untreated. For those younger than 65, the cumulative incidence of death at 90 days was 0.04% (95% CI, 0.02% to 0.11%) for the treated and 0.32% (95% CI, 0.25% to 0.40%) for the untreated.
Older age, male sex, and low socioeconomic status were tied to a higher risk of death for Paxlovid recipients. Patients who had weakened immune systems, cardiovascular diseases, or other nonrespiratory diseases also were at higher risk of death. Vaccination and previous infection were linked to a lower risk of death.
Among molnupiravir recipients, the cumulative risk of death at 90 days was 0.60% (95% CI, 0.41% to 0.88%) for treated patients and 1.57% (95% CI, 1.43% to 1.68%) for the untreated. Among patients aged 65 or older, the incidence of death was 0.88% (95% CI, 0.59% to 1.31%) for the treated and 3.46% (95% CI, 3.12% to 3.71%) for the untreated. Among those younger than 65, the incidence of death was 0.17% (95% CI, 0.05% to 0.54%) for the treated and 0.44% (95% CI, 0.36% to 0.53%) for untreated patients.
The adjusted HR of death among molnupiravir recipients was 0.23 (95% CI, 0.16 to 0.34). Among patients 65 years or older, the adjusted HR was 0.24 (95% CI, 0.16 to 0.37). Among younger patients, the adjusted HR was 0.13 (95% CI, 0.04 to 0.43).
"These findings suggest that the use of either nirmatrelvir or molnupiravir is associated with reductions in mortality and hospitalization in patients infected with Omicron, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions," the study authors wrote. "Both drugs can, therefore, be used to treat nonhospitalized patients who are at high risk of progressing to severe COVID-19."
Paxlovid had slight advantage against death
In eClinicalMedicine, University of Hong Kong researchers compare the effectiveness of Paxlovid and molnupiravir in nonhospitalized and hospitalized COVID-19 patients.
The team analyzed data from a territory-wide electronic health records database from adults who tested positive for COVID-19 and were prescribed molnupiravir or Paxlovid from March to December 2022. Participants included 63,522 nonhospitalized adults (31,761 each received Paxlovid and molnupiravir) and 11,784 hospitalized (5,892 each received Paxlovid and molnupiravir).
Among outpatients, 336 died of any cause, and 162 were admitted to the intensive care unit (ICU) or required ventilation (ICU; Paxlovid, 0.22%; molnupiravir, 0.29%), and 4,890 were hospitalized (Paxlovid, 5.83%; molnupiravir, 9.56%).
When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option.
Compared with molnupiravir users, Paxlovid recipients had lower risks of all-cause death (absolute risk reduction [ARR] at 28 days, 0.61%; HR: 0.43) and hospitalization (ARR at 28 days, 3.73%; HR, 0.72).
Among hospitalized patients, 509 died of any cause (Paxlovid, 2.99%; molnupiravir, 5.65%), and 50 patients were admitted to the ICU or needed ventilation (Paxlovid, 0.44%; molnupiravir, 0.41%). Compared with molnupiravir recipients, those prescribed Paxlovid had lower rates of all-cause death (ARR at 28 days, 2.66%; HR, 0.59).
In both settings, there were no between-group differences in the risk of ICU admission or ventilation.
"Our analyses suggest that nirmatrelvir-ritonavir was more effective than molnupiravir in reducing the risk of all-cause mortality in both non-hospitalised and hospitalised patients," the authors wrote. "When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option."