Real-World Effectiveness of Nirmatrelvir-Ritonavir in Preventing Coronavirus Disease 2019–Associated Hospitalization: A Population-Based Cohort Study in the Province of Québec, Canada

BACKGROUND: The nirmatrelvir-ritonavir has shown to reduce coronavirus disease 2019 (COVID-19) hospitalization and death before the Omicron era, but updated real-world evidence studies are needed. The current study aimed to assess whether nirmatrelvir-ritonavir reduces the risk of COVID-19-associated hospitalization among high-risk outpatients. METHODS: This was a retrospective cohort study of severe acute respiratory syndrome coronavirus 2-infected outpatients between 15 March and 15 October 2022, using data from the Québec clinico-administrative databases. Propensity score matching was used to compare infected outpatients treated with nirmatrelvir-ritonavir with those not receiving nirmatrelvir-ritonavir. The relative risk (RR) of COVID-19-associated hospitalization occurring within 30 days following the index date was assessed using a Poisson regression. RESULTS: A total of 14 756 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir-ritonavir treatment was associated with a 74% reduced RR of hospitalization (RR, 0.26 [95% confidence interval [CI], .23-.29]; number needed to treat [NNT, 15). The effect was more pronounced in outpatients with an incomplete primary vaccination course (RR, 0.13 [95% CI, .08-.20]; NNT, 9). Benefit was also found in those with a complete primary vaccination course (RR, 0.28 [95% CI, .25-.32]; NNT, 17) regardless of age and the delay since the last vaccination. Subgroups analysis among high-risk outpatients with a primary vaccination course showed that nirmatrelvir-ritonavir treatment was associated with a significant decrease in the RR of hospitalization in severely immunocompromised outpatients (RR, 0.28 [95% CI, .21-.36]; NNT, 7), regardless of the delay since the last vaccination. CONCLUSIONS: Nirmatrelvir-ritonavir reduces the risk of COVID-19-associated hospitalization among incompletely and completely vaccinated high-risk outpatients, as well as immunocompromised individuals, regardless of age and the delay since the last vaccination.