Clinical Question

Does nirmatrelvir/ritonavir (Paxlovid) improve outcomes in a largely vaccinated population of patients with COVID-19?

Bottom Line

Paxlovid reduces hospitalization and mortality in older, high-risk patients with COVID-19, but data in younger vaccinated patients are inconsistent. More studies are needed, particularly in patients 50 to 64 years of age. (Level of Evidence = 2b)

Synopsis

The primary study used to approve Paxlovid for use in out-patients with COVID-19 included only high-risk unvaccinated patients. The most recent study from a large health system in Israel identified adults 40 years and older who were eligible to receive the drug during the Omicron surge. It compared patients who received Paxlovid within five days of a confirmed diagnosis of COVID-19 with patients who did not. Overall, 78% of included patients had previous immunity by vaccination, prior infection, or both. The analysis was adjusted for comorbidities, demographics, ethnicity, religious affiliation, and socioeconomic status. Approximately 80% of participants were considered fully vaccinated. Data were stratified by age, and benefit was only seen in people 65 years and older. The rate of hospitalization (14.7 vs. 58.9 cases per 100,000 person-days; adjusted hazard ratio [HR] = 0.27; 95% CI, 0.15 to 0.49) and the risk of death (HR = 0.21; 95% CI, 0.05 to 0.82) were lower in this group. There was no difference in either outcome in patients 40 to 64 years of age. Past research has shown a higher overall risk for patients older than 50 years, but results for patients 50 to 64 years of age were not reported in this study. A second study from Hong Kong compared outcomes in outpatients given Paxlovid with those who were not treated. This study found lower rates of mortality (HR = 0.25; 95% CI, 0.13 to 0.47) and hospitalization (HR = 0.69; 95% CI, 0.60 to 0.79) in patients given Paxlovid. The study found no difference in benefit by age, although only approximately 20% of the patients in the study were younger than 65 years, and only 35% were fully vaccinated.