Hospitalized COVID-19 patients treated with the antiviral drug nirmatrelvir–ritonavir (Paxlovid) are at lower risk for death, intensive care unit (ICU) admission, and need for ventilation than those given a combination of Paxlovid and the antiviral drug remdesivir (Veklury) or Veklury alone, a University of Hong Kong target trial emulation study suggests.
For the study, published yesterday in The Lancet Infectious Diseases, the researchers analyzed the electronic health records of a weighted sample of adults hospitalized for COVID-19 who received either Paxlovid plus Veklury (18,410 patients) or either drug alone (18,178 for Veklury, 18,287 for Paxlovid) within 5 days of hospitalization from March 16 to Dec 31, 2022.
The study period spanned SARS-CoV-2 Omicron variant predominance. Median follow-up was 84 days, and the average age of participants was 75 years.
Both Veklury and Paxlovid are prescribed for patients with mild or moderate COVID-19 at risk for severe disease, but Paxlovid is not given to many hospitalized patients because of contraindications.
Risk of ICU admission, need for ventilation
In total, 7,050 participants died of any cause (cumulative incidence, 12.9%; Veklury alone, 20.5%; Paxlovid alone, 4.2%; and combination therapy, 14.0%). There were also 3,688 ICU admissions or ventilations (cumulative incidence, 6.7%; Veklury alone, 11.2%; Paxlovid alone, 1.1%; and combination treatment, 7.9%).
The risk of death was lower in recipients of Paxlovid only (hazard ratio [HR], 0.18; absolute risk reduction [ARR], –16.3%) or a combination of Veklury and Paxlovid (HR, 0.66; ARR, –6.5%) than in those given Veklury alone.
Findings were comparable for ICU admission or ventilation (Paxlovid alone HR, 0.09; ARR, –10.0% and combination therapy HR, 0.68; ARR, –3.2%). Relative to combination therapy, Paxlovid monotherapy was tied to a much lower risk of death (HR, 0.27; ARR, –9.8%) and ICU admission or ventilation (HR, 0.13; ARR, –6.8%).
Recipients of Paxlovid alone had a significantly reduced risk of heart attack, acute kidney injury, anemia, hyperglycemia, and abnormal blood clotting than those receiving Veklury alone. Patients given combination treatment had a significantly lower risk of abnormal clotting than those receiving Veklury alone. The cumulative incidence of common adverse events such as ischemic stroke, rash, gastrointestinal symptoms, and hypoglycemia was similar regardless of treatment type.
Clear criteria needed for in-hospital Paxlovid
"Early initiation of nirmatrelvir–ritonavir monotherapy within 5 days of COVID-19 confirmation led to a significant decrease in all-cause mortality risk and a favourable safety profile," the researchers wrote. "These benefits were consistent across differing COVID-19 vaccination statuses, admission criteria, respiratory support modalities, and underlying comorbidities."
"Randomised controlled trials are needed to support the validity of the current results and to investigate the efficacy and safety of combination therapy with nirmatrelvir–ritonavir and remdesivir or other antiviral combinations," they concluded.
If nirmatrelvir–ritonavir is to be recommended as inpatient therapy for treating high-risk hospitalised patients with COVID-19, then clear criteria should be established as to its use, especially in terms of defining and identifying the target population.
In a related commentary, Karolina Akinosoglou, MD, PhD, and Charalambos Gogos, MD, PhD, both of the University of Patras in Greece, said the study findings could represent an opportunity to improve hospital COVID-19 treatment guidelines with the inclusion of Paxlovid.
"However, if nirmatrelvir–ritonavir is to be recommended as inpatient therapy for treating high-risk hospitalised patients with COVID-19, then clear criteria should be established as to its use, especially in terms of defining and identifying the target population," they wrote.
