Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications

Key Points

Question

What is the association of nirmatrelvir and ritonavir exposure with the risk of death or COVID-19–related hospitalization when accounting for patient vulnerability to complications from COVID-19 infection?

Findings

In this cohort study of 6866 individuals with COVID-19, treatment with nirmatrelvir and ritonavir was associated with lower risk of death or hospitalization in the most clinically extremely vulnerable individuals but not in less vulnerable individuals. Individuals who were not extremely vulnerable to experiencing complications from COVID-19, whose median age was 79 years, had greater risk of the outcome while receiving nirmatrelvir and ritonavir, but the finding was not statistically significant.

Meaning

In this study, treatment with nirmatrelvir and ritonavir was not associated with reduced risk of death or hospitalization among individuals who were not extremely vulnerable to complications from COVID-19 infection, regardless of age.

Abstract

This cohort study examines the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection.

Abstract

Importance

Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials.

Objective

To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection.

Design, Setting, and Participants

This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated.

Exposures

Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir.

Main Outcomes and Measures

The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.

Results

There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], −2.5%, 95% CI, −4.8% to −0.2%) and the CEV2 group (2628 patients; RD, −1.7%; 95% CI, −2.9% to −0.5%). In the CEV3 group, the RD was −1.3%, but the findings were not statistically significant (2100 patients; 95% CI, −2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, −0.9% to 2.9%).

Conclusions and Relevance

In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.