Research Program Manager University of British Columbia Victoria, Canada
Background: In February 2022, British Columbia residents at higher risk of severe outcomes from Covid-19 infection were granted eligibility to receive Nirmatrelvir and ritonavir (NMVr; Paxlovid). Post-market analysis of these patients is essential because eligibility criteria for NMV-r differed substantially from participants in published clinical trials.
Objectives: Determine if NMVr in clinically extremely vulnerable (CEV) individuals with Covid-19 in British Columbia was associated with a reduced risk of Covid-19-related emergency admission to hospital or death.
Methods: We undertook a cohort study of adult patients in British Columbia, Canada, using anonymized and linkable Ministry of Health datasets for prescriptions, hospitalizations, emergency department encounters, physician visits, Covid-19 PCR testing, and Covid-19 vaccination. Patients were eligible for the study if they belonged to one of 4 vulnerable groups who received priority for Covid-19 vaccination. Two groups included people who were severely (CEV1), or moderately (CEV2) immunocompromised. CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from Covid-19. A fourth Expanded Eligibility group (EXEL) was added in March 2022 to allow wider access to NMV-r for some higher-risk individuals not captured in the other groups. Covid-19-positive patients who started NMVr were matched to patients in the same vulnerability group, who were of the same sex, age (+/-2 years), propensity score, and who were also infected within one month of the NMVr treated individual. The primary endpoint was Covid-19-related emergnecy hospitalization or death from any cause within 28 days of cohort entry.
Results: AIn interim analyses, there were 54,498 individuals in the CEV and EXEL groups between February and September of 2022, of which 10,939 (20%) were prescribed NMVr. 6,148 individuals were included in 4 cohorts with 1:1 matching of NMVr exposed and unexposed individuals. Compared with unexposed controls, treatment with NMV-r was associated with statistically significant relative reductions in the primary endpoint in the CEV1 (n=526; HR 0.18, 95%CI 0.04-0.80) and CEV3 groups (n=1,934; HR 0.22; 95%CI 0.07-0.65). We found a non-significant reduction in the CEV2 group (n=2,408; HR 0.59; 95%CI 0.32-1.10), and a non-significant increase in risk in the EXEL group (n=1,280; HR 1.70; 95%CI 0.68-4.40).
Conclusions: The study found that NMVr treatment was associated with reduced risk of Covid-19 hospitalization or death in clinically extremely vulnerable (CEV) individuals in British Columbia, with the greatest benefit observed in severely immunocompromised individuals, but no reduction observed in lower-risk individuals.