Effectiveness of Subcutaneous Casirivimab and Imdevimab Relative to no COVID-19 Antibody Treatment Among Patients Diagnosed With COVID-19 in the Ambulatory Setting

Importance Data on real-world effectiveness of subcutaneous (SC) administration of casirivimab and imdevimab (CAS+IMD) for treatment of COVID-19 are limited. Objective To assess effectiveness of SC CAS+IMD vs no COVID-19 antibody treatment among patients diagnosed with COVID-19 in ambulatory settings during the Delta-dominant period prior to Omicron emergence. Design Retrospective cohort study. Setting Encrypted linked data between Komodo Health closed claims database and CDR Maguire Health & Medical database. Participants Patients with COVID-19 in ambulatory settings between August 1, 2021 and October 30, 2021 treated with SC CAS+IMD were exact- and propensity score-matched to up to 5 untreated patients who were treatment-eligible under the Emergency Use Authorization (EUA) Exposure Subcutaneous CAS+IMD. Main Outcomes and Measures Composite endpoint of 30-day all-cause mortality or COVID- 19-related hospitalization. Kaplan-Meier estimators were used to calculate composite risk overall and across subgroups including age, COVID-19 vaccination status, immunocompromised, and elevated risk defined as age ≥ 65 years or 55-64 years with body mass index ≥ 35 kg/m[2][1], type 2 diabetes, chronic obstructive pulmonary disease, or chronic kidney disease. Cox proportional- hazards models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results Among 13 522 patients treated with SC CAS+IMD, 12 972 (95.9%) were matched to 41 848 EUA-eligible untreated patients; patients were 57-58% female, with mean age between 50 and 52 years. The 30-day composite outcome risk was 1.9% (95% CI, 1.7-2.2; 247 events) and 4.4% (95% CI, 4.2-4.6; 1822 events) in the CAS+IMD-treated and untreated cohorts, respectively; CAS+IMD treatment was associated with a 49% lower risk (aHR 0.51; 95% CI, 0.46-0.58). Treatment was also associated with a 67% lower 30-day risk of all-cause mortality (aHR 0.33, 95% CI, 0.18-0.60). Treatment effectiveness was consistent regardless of vaccination status and across subgroups, including those at elevated risk (aHR 0.51, 95% CI 0.42-0.60) or immunocompromised (aHR 0.34, 95% CI 0.17-0.66). Conclusions and Relevance Subcutaneous treatment with CAS+IMD is effective for reducing all-cause mortality or COVID-19-related hospitalization in patients diagnosed with COVID-19 and managed in real-world outpatient settings during the Delta-dominant period. Effectiveness is maintained among immunocompromised, vaccinated, and elevated risk patients. ### Competing Interest Statement J.J. Jalbert, M. Hussein, V. Mastey, R.J. Sanchez, D. Wang, D. Murdock, B. Hirshberg, D.M. Weinreich, and W. Wei are employees and stockholders of Regeneron Pharmaceuticals, Inc. L. Farinas, J. Bussey, and C. Duart report no conflicts. ### Funding Statement This work was supported by Regeneron Pharmaceuticals, Inc. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The authors conducted secondary research using de-identified data licensed from a third party, Komodo, in compliance with 45 CFR 164.514(a)-(c). The data had identifying patient information removed and were coded in such a way that the data could not be linked back to subjects from whom they were originally collected prior to the authors gaining access to it. This research, which used the de-identified licensed data described above, does not require IRB or ethics review, as analyses with these data do not meet the definition of 'research involving human subjects' as defined within 45 CFR 46.102(f) which stipulates human subjects as living individuals about whom an investigator obtains identifiable private information for research purposes. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data generated or analyzed during this study are included in this published article. [1]: #ref-2