Abstract: medRxiv preprint doi: https://doi.org/10.1101/2022.02.28.22270796; this version posted February 28, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Real-world Effectiveness of Casirivimab and Imdevimab in Patients With COVID-19 in the Ambulatory Setting: An Analysis of Two Large US National Claims Databases Wenhui Wei, Dana Murdock, Jessica J. Jalbert, Vera Mastey, Robert J. Sanchez, Boaz Hirshberg, David M. Weinreich, Mohamed Hussein Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY Corresponding to: Wenhui Wei, PhD, Email: wenhui.wei@regeneron.com Alternate corresponding author: Mohamed Hussein, PhD, Email: mohamed.hussein@regeneron.com 1 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2022.02.28.22270796; this version posted February 28, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Abstract Background: In a phase III clinical trial, casirivimab and imdevimab (CAS+IMD) reduced the composite endpoint of COVID-19-related hospitalizations or all-cause mortality in outpatients at risk of severe disease. This study assessed real-world effectiveness of CAS+IMD. Methods: Data from Optum® Clinformatics® Data Mart (CDM) and IQVIA Pharmetrics Plus (PMTX+) were used to identify patients diagnosed with COVID-19 in ambulatory settings between December 2020 and March 2021 (PMTX+) and June 2021 (CDM), and either treated with CAS+IMD or untreated but treatment-eligible under Emergency Use Authorization. CAS+IMD-treated patients were matched to untreated patients and followed up to 30 days for the outcome of all-cause mortality or COVID-19-related hospitalizations (CDM) and COVID-19-related hospitalizations (PMTX+). Kaplan-Meier estimators were used to calculate outcome risks; Cox proportional-hazard models estimated adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Results: For CDM, 1116 CAS+IMD-treated patients were matched to 5294 untreated patients; for PMTX+, 3280 CAS+IMD-treated patients were matched to 16,284 untreated patients. The 30-day outcome risk was 2.1% and 5.3% in treated and untreated cohorts, respectively (CDM), and the 30-day risk of COVID-19-related hospitalization was 1.9% and 4.8%, respectively (PMTX+); translating to a 61% lower adjusted outcome risk (CDM aHR 0.39 (95% CI 0.26–0.60; PMTX+ aHR 0.39 (95% CI 0.30–0.51). The benefit of treatment was maintained across multiple subgroups of highrisk patients; earlier intervention was associated with improved outcomes. 2 medRxiv preprint doi: https://doi.org/10.1101/2022.02.28.22270796; this version posted February 28, 2022. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Conclusions: This real-world study further supports randomized clinical trial findings that treatment with CAS+IMD reduces the risk of hospitalization and mortality in..