Real-World Effectiveness of Nirmatrelvir/Ritonavir in Preventing Hospitalization Among Patients With COVID-19 at High Risk for Severe Disease in the United States: A Nationwide Population-Based Cohort Study

Abstract

Objectives: The aim of this analysis was to describe nirmatrelvir/ritonavir real-world effectiveness in preventing hospitalization among high-risk US COVID-19 patients during SARS-CoV-2 Omicron predominance. Design: An ongoing population-based cohort study with retrospective and prospective collection of electronic healthcare data in the United States. Methods: Data for this analysis were collected from the US Optum de-identified COVID-19 Electronic Health Record (EHR) dataset during December 22, 2021 to June 8, 2022. Key eligibility criteria for inclusion in the database analysis were at least 12-years-old; positive SARS-CoV-2 test, COVID-19 diagnosis, or nirmatrelvir/ritonavir prescription; and high risk of severe COVID-19 based on demographic/clinical characteristics. Potential confounders between groups were balanced using propensity score matching (PSM). Immortal time bias was addressed. Outcome measures: Hospitalization rates within 30 (primary analysis) or 15 (sensitivity analysis) days from COVID-19 diagnosis overall and within subgroups were evaluated. Results: Before PSM, the nirmatrelvir/ritonavir group (n=2811) was less racially diverse, older, and had higher COVID-19 vaccination rates and a greater number of comorbidities than the non-nirmatrelvir/ritonavir group (n=194,542). Baseline characteristics were well balanced across groups (n=2808 and n=10,849, respectively) after PSM. Incidence of hospitalization (95% CI) within 30 days was 1.21% (0.84%, 1.69%) for the nirmatrelvir/ritonavir group and 6.94% (6.03%, 7.94%) for the non-nirmatrelvir/ritonavir group, with a hazard ratio (95% CI) of 0.16 (0.11, 0.22; 84% relative risk reduction). Incidence within 15 days was 0.78% (0.49%, 1.18%) for the nirmatrelvir/ritonavir group and 6.54% (5.65%, 7.52%) for the non-nirmatrelvir/ritonavir group; hazard ratio 0.11 (0.07, 0.17; 89% relative risk reduction). Nirmatrelvir/ritonavir was effective in African American patients (hazard ratio, 0.35 [0.15, 0.83]; 65% relative risk reduction). Relative risk reductions were comparable with overall results across ages and among vaccinated patients. Conclusions: Real-world nirmatrelvir/ritonavir effectiveness against hospitalization during the Omicron era supports EPIC-HR efficacy among high-risk patients. Future research should confirm these early real-world results and address limitations.

Efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) for COVID‐19: A rapid review and meta‐analysis

“…Thirteen studies 6–8,17–20,22–25,29,34 involving 298 913 patients were included in the meta‐analysis. The pooled estimate showed a significant difference in the mortality rate of Paxlovid‐recieving patients compared to those who not received Paxlovid (OR = 0.25; 95% CI: 0.14–0.45; p = 0.000) (Figure 2A).…”

“…The results of the risk of bias in the included studies are shown in Supporting Information: Tables S1 and S2. Thirteen studies [6][7][8][17][18][19][20][22][23][24][25]29,34 involving 298 913 patients were included in the meta-analysis. The pooled estimate showed a significant difference in the mortality rate of Paxlovid-recieving patients compared to those who not received Paxlovid (OR = 0.25; 95% CI: 0.14-0.45; p = 0.000) (Figure 2A).…”

Effectiveness of Nirmatrelvir-Ritonavir for the treatment of patients with mild to moderate COVID-19 and at high risk of hospitalization: Systematic review and meta-analyses of observational studies

“…Thirteen studies reported mortality data, including 1,159,467 patients and 7,133 deaths (11,13–19,21–25). In comparison to standard treatment without antivirals, nirmatrelvir-ritonavir reduced the risk of death by 62% (OR= 0.38; 95% CI: 0.30-0.46; moderate certainty of evidence) (Fig 2).…”

“…Eleven studies reported data on hospitalization within 35 days of follow-up after the initiation of the treatment, which included 963,626 patients, with the occurrence of 11,903 events (11–13,17–19,21–25)…”

“…The sixteen studies finally considered were conducted in 5 countries (Canada, China, United States, Israel, and United Kingdom). Of these, as of the last update of the search, 12 studies were published (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and 4 were unpublished studies (preprint) (23)(24)(25)(26). All studies were retrospective cohorts of data obtained from electronic records of hospitals and other healthcare centers, collected from January 2021 to October 2022.…”