Effect of Early Administration of Casirivimab and Imdevimab in Hospitalized Patients with COVID-19: A Post Hoc Analysis

Purpose: Casirivimab and imdevimab (CAS+IMD) has been shown to improve clinical outcomes (death/mechanical ventilation) in seronegative hospitalized patients with COVID-19. The objective of the current analysis was to assess whether time to administration of CAS+IMD, from the start of COVID-19 symptoms, influenced these outcomes. Patients and Methods: This was a post hoc analysis of Study 2066 (conducted between 10 June 2020 and 9 April 2021), a Phase I/II/III trial investigating the safety and efficacy of CAS+IMD (single intravenous dose) vs placebo in hospitalized adult patients with COVID-19. The primary outcome in this analysis was death or mechanical ventilation. Two populations of patients were assessed: efficacy (n = 738) and exploratory (full analysis set-exploratory data analysis [FAS-EDA]; n = 1115). Time to administration was defined as the number of days of COVID-19 prior to treatment, 4 days being the first quartile, which was considered early treatment administration of CAS+IMD. Results: Odds of death or mechanical ventilation were higher in those aged 50– 70 years (odds ratio [OR]: 2.98; 95% confidence interval [CI], 1.62– 5.91; P = 0.0008) and > 70 years (OR: 4.50; 95% CI, 2.45– 8.96; P = 0.001) than those aged < 50 years. Overall, patients who received CAS+IMD < 4 days after first COVID-19 symptoms had better outcomes than patients receiving CAS+IMD ≥ 4 days, on adjusted analyses (efficacy OR: 0.42; 95% CI, 0.20– 0.80; P = 0.0122; FAS-EDA OR: 0.63; 95% CI, 0.38– 1.01; P = 0.0664). These differences were most notable in those aged 50– 70 years (OR: 0.24; 95% CI, 0.05– 0.70; P = 0.0219). Conclusion: Early monoclonal antibody treatment is associated with better outcomes in hospitalized patients with severe COVID-19.