In the omicron phase of the COVID-19 pandemic in a mostly vaccinated population, is nirmatrelvir-ritonavir still effective at reducing hospitalizations and death in outpatients?
In this well-done propensity score matched study, Paxlovid continues to provide a clinically meaningful reduction in hospitalizations and mortality, especially for the less vaccinated and for adults older than 70 years. This is the third methodologically sound study to come to this conclusion. In the absence of randomized trials, this represents our best available evidence.
Plan de l'etude:
The only published randomized trial of nirmatrelvir-ritonavir (Paxlovid) for outpatients with COVID-19 was done in a relatively high-risk and unvaccinated population while the ancestral variant was predominant. Previous observational studies in Israel and Hong Kong both found persistent benefit, especially in older adults. This Canadian study linked several databases (pharmacy, insurance, vaccination) to create a dataset with information on 177,545 patients with acute COVID-19, of whom 8876 had received Paxlovid. The patients' age range was 18 to 110 years, and the data were from April to August of 2022. The authors excluded those admitted to hospital, those with nosocomial infection, and non-Ontarians. Among the patients who received the medication, 72.5% were older than 70 years, 85% had 3 or more vaccines, and 57% had fewer than 3 comorbidities. The authors used propensity score matching to identify patients who were alike with regard to age, sex, vaccination status, and comorbidities, but who differed with regard to whether they received Paxlovid. The groups who did and did not receive Paxlovid were quite different, but the propensity score matching is a good way to adjust for those differences. Overall, the use of Paxlovid reduced the likelihood of hospitalization or death in the weighted analysis (2.1% vs 3.7%; odds ratio [OR] 0.56; 95% CI 0.47 - 0.67; number needed to treat [NNT] = 62). Mortality alone was also significantly lower (OR 0.49; 0.40 - 0.60). Subgroup analyses found generally similar reductions in risk by age, vaccination, and the number of comorbidities. However, the absolute risk reduction and NNT were more favorable for patients older than 70 (NNT = 45) and for those who had fewer than 3 vaccinations (NNT = 28 - 30).
Mark H. Ebell, MD, MS
University of Georgia