EFFECTIVENESS OF CASIRIVIMAB-IMDEVIMAB AND SOTROVIMAB MONOCLONAL ANTIBODY TREATMENT AMONG HIGH-RISK PATIENTS WITH SARS-CoV-2 INFECTION: A REAL-WORLD EXPERIENCE (preprint)

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can evade neutralizing antibodies, raising concerns about the effectiveness of anti-spike monoclonal antibodies (mAb). METHODS: This study reports a retrospective data analysis in Banner Health Care System. Out of 109,788 adult patients who tested positive for COVID-19, the study cohort was split into patients who received Casirivimab-Imdevimab (Cas-Imd) (N=10,836; Delta-predominant period 6/2021-11/2021) and Sotrovimab (N=998; Omicron-predominant period 12/2021-1/2022) mAb compared to propensity-matched control groups (N=10,836 and N=998), respectively. Index date was the date of mAb administration or the date of positive COVID-19 testing. The primary and secondary outcomes were the incidence of composite outcome (all-cause hospitalization and/or mortality) and ICU admission at 30-days following index date, respectively. RESULTS: Compared to the propensity-matched untreated control cohort, the Cas-Imd mAb reduced the composite outcome (from 7.5% to 3.7%; difference: -3.8% [95% CI: (-4.4%, -3.2%)], p <0.01) regardless of their vaccination status, while Sotrovimab mAb did not (5.0% vs. 3.8%; difference: -1.2% [95% CI: (-3.1%, 0.7%)], p =0.22). In terms of the secondary outcome, similarly Cas-Imd mAb decreased ICU admission during the first hospitalization (from 1.5% to 0.5%; difference: -1.0% [95% CI: (-1.3%, -0.7%)], p <0.01) compared to the control group, whereas Sotrovimab mAb did not (0.9% vs. 0.6%; difference: -0.3% [95% CI: (-1.2%, 0.6%)], p =0.61). Comparing the periods, the Omicron-predominant period was associated with lower composite outcome than that during the Delta-predominant period. CONCLUSIONS: Cas-Imd mAb was effective against the SARS-CoV-2 Delta variant, however sotrovimab lacked efficacy in patients with SARS-CoV-2 Omicron-predominant period.

Lack of effectiveness of Bebtelovimab Monoclonal Antibody Among High-Risk Patients with SARS-Cov-2 Omicron During BA.2, BA.2.12.1 and BA.5 Subvariants Dominated Era (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants are expected to be resistant to Bebtelovimab (BEB) monoclonal antibody (MAb) and the real-world experience regarding its effectiveness is scarce. This retrospective cohort study reports a data analysis in Banner Healthcare System (a large not-for-profit organization) between 4/5/2022 and 8/1/2022 and included 19,778 Coronavirus disease-19 (COVID-19) positive (by PCR or direct antigen testing) patients who were selected from Cerner-Electronic Health Record after the exclusions criteria were met. The study index date for cohort was determined as the date of BEB MAb administration or the date of the first positive COVID-19 testing. The cohort consist of COVID-19 infected patients who received BEB MAb (N=1,091) compared to propensity score (PS) matched control (N=1,091). The primary outcome was the incidence of 30-day all-cause hospitalization and/or mortality. All statistical analyses were conducted on the paired (matched) dataset. For the primary outcome, the event counts and percentages were reported. Ninety-five percent Clopper-Pearson confidence intervals for percentages were computed. The study cohorts were 1:1 propensity matched without replacement across 26 covariates using an optimal matching algorithm that minimizes the sum of absolute pairwise distance across the matched sample after fitting and using logistic regression as the distance function. The pairs were matched exactly on patient vaccination status, BMI group, age group and diabetes status. Compared to the PS matched control group (2.6%; 95% confidence interval [CI]: 1.7%, 3.7%), BEB MAb use (2.2%; 95% CI: 1.4%, 3.3%) did not significantly reduce the incidence of the primary outcome (p=0.67). In the subgroup analysis, we observed similar no-difference trends regarding the primary outcomes for the propensity rematched BEB MAb treated and untreated groups, stratified by patient vaccination status, age (<65 years or [≥]65), and immunocompromised status (patients with HIV/AIDS or solid organ transplants or malignancy including lymphoproliferative disorder). The number needed to treat (1/0.026-0.022) with BEB MAb was 250 to avoid one hospitalization and/or death over 30 days. The BEB MAb use lacked efficacy in patients with SARS-CoV-2 Omicron subvariants (mainly BA.2, BA.2.12.1, and BA.5) in the Banner Healthcare System in the Southwestern United States.