(084) A Cohort Study to Evaluate the Real-World Utilization and Effectiveness of Bebtelovimab Compared to Nirmatrelvir/Ritonavir among Patients with Mild-to-Moderate COVID-19 Who Are at High Risk for Progressing to Severe Illness

Background: Bebtelovimab (BEB) received US FDA emergency use authorization on 11 February 2022 for COVID-19 treatment and was de-authorized on 30 November 2022. An observational study was conducted to assess the effectiveness of BEB during a period before the BEB-resistant Omicron subvariants BQ.1 and BQ.1.1 became predominant in the US.

Objectives: To evaluate whether intravenous BEB was non-inferior to oral nirmatrelvir/ritonavir (NR) for treatment of mild-to-moderate COVID-19 patients who were at high risk for progressing to severe illness.

Methods: We conducted a new-user, cohort study with an active comparator. Data were derived from de-identified electronic health records of a federated network of health care organizations in the US (TriNetX Dataworks USA). Exposures included treatment with BEB or NR. Non-hospitalized patients aged 12 years or older on first BEB administration or NR dispensing (index date) from 16-Feb-22 through 31-Aug-22 were eligible. Follow-up began the day after index date and continued up to 30-days, using an intent to treat approach. The primary outcome was the composite of all-cause hospitalization or all-cause mortality. Coarsened exact and high-dimensional propensity score matching were used to control for confounding. Risk differences and corresponding 95% confidence interval (95% CI) were calculated. The pre-defined non-inferiority margin was 1.795%.

Results: A total of 12,920 BEB and 70,741 NR users were identified. Baseline demographic and clinical characteristics indicated the presence of channeling, with patients administered BEB being older and having more co-morbidities. Coarsened exact and propensity score matching resulted in 5,827 pairs that were well-balanced with respect to baseline characteristics. The median age was 65 years (interquartile range: 50 – 74). Patients were primarily female and White. Common baseline comorbidities included hypertension, obesity, type 2 diabetes, hematologic or solid malignancy except basal cell carcinoma, depression, and chronic kidney disease. Administration of COVID-19 treatments during follow-up was uncommon ( < 5% for both cohorts). The 30-day cumulative incidence of all-cause hospitalization or mortality was 2.03% (95% CI: 1.68%, 2.42%) among BEB users and 1.84% (95% CI: 1.51%, 2.21%) among NR users. The BEB vs. NR risk difference was 0.19% (95% CI: -0.31%, 0.69%).

Conclusions: Patients exposed to BEB were older and had more co-morbidities versus those exposed to NR. Differences were successfully addressed by matching methods. Based on the a priori specified non-inferiority margin, BEB was not inferior to NR with respect to 30-day all-cause hospitalization or death in a real-world clinical setting.