Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Ambulatory Patients with Early COVID-19
Authors: Webb Brandon J. , Buckel Whitney , Vento Todd , Butler Allison M. , Grisel Nancy , Brown Samuel M. , Peltan Ithan D. , Spivak Emily S. , Shah Mark , Sakata Theadora , Wallin Anthony , Stenehjem Eddie , Poulsen Greg , Bledsoe Joseph 
Published: March 2021

Importance

Interventions to reduce hospitalization of patients with COVID-19 are urgently needed. Randomized trials for efficacy suggest that anti-SARS-CoV2 neutralizing monoclonal antibodies (MAb) may reduce medically-attended visits and hospitalization but effectiveness has not been confirmed in a real-world setting.

Objective

Estimate the effectiveness of MAb infusion in a real-world cohort of ambulatory patients with early symptomatic COVID-19 at high risk for hospitalization.

Design

Quasi-experimental observational cohort study using target trial emulation and causal inference methodology in pre-and post-implementation groups.

Setting

Infusion centers and urgent care clinics within an integrated healthcare system in the United States

Participants

13,534 high-risk adult outpatients with symptomatic, laboratory-confirmed COVID-19 within 7 days of symptom onset.

Exposures

A single intravenous infusion of either bamlanivimab 700 mg or casirivimab/imdevimab 1200 mg/1200 mg.

Main Outcomes and Measures

The primary outcome was emergency department visit or hospitalization within 14 days of positive test. Patients who received MAb infusion were compared to contemporaneous controls using inverse probability of treatment weighting, and to a pre-implementation cohort using propensity-weighted interrupted time series analysis. An exploratory analysis compared effectiveness of casirivimab/imdevimab and bamlanivimab.

Results

7404 patients who would have been MAb-eligible were identified in a pre-implementation cohort (July 1-November 27, 2020). In the post-implementation period (November 28, 2020-January 28, 2021), 594 received MAb treatment and 5536 MAb-eligible patients did not. Among Mab recipients, 479 (80.6%) received bamlanivimab and 115 (19.4%) casirivimab/imdevimab. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) patients in the pre-implementation cohort. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio estimating the average treatment effect 0.69, 95% CI 0.60-0.79). After implementation, propensity-weighted probability of emergency department visit or hospitalization decreased by 0.7% per day (95% CI 0.03-0.10%, p<0.001). Overall, 7 (1.2%) MAb patients experienced an adverse event; two (0.3%) were considered serious. In the exploratory analysis, the effect of casirivimab/imdevimab versus bamlanivimab was not significant (OR 0.52, 95% CI 0.17-1.63, p=0.26).

Conclusions and Relevance

MAb treatment of high-risk ambulatory patients with early COVID-19 was well-tolerated and effective at preventing the need for subsequent medically-attended care.

Key Points Section

Question

What is the real-world effectiveness of COVID-19 monoclonal neutralizing antibody (MAb) infusions in high-risk, ambulatory patients?

Findings

594 high-risk, early-symptomatic adults with COVID-19 treated with MAb infusion were compared to 5536 contemporaneous controls using inverse probability of treatment weighting, and to 7404 patients in a pre-implementation cohort using propensity-weighted interrupted time series analysis. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio 0.69 (95% CI 0.60-0.79). After MAb implementation the probability of emergency department visit or hospitalization decreased by 0.7% per day, 95% CI 0.03-0.10%, p<0.001).

Meaning

Monoclonal antibody infusion within seven days of symptom onset in high-risk ambulatory adults with COVID-19 appears to prevent subsequent emergency department visits and hospitalization. Further evaluation of the differences between specific Mab products is warranted.