Abstract
Objectives: Comparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta.
Methods: Allocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7.Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period.
Results: COVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p<0.001) on D7.
Conclusions: In a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response.
Keywords: COVID-19; SARS-COV-2; bamlanivimab/etesevimab; casirivimab/imdevimab; early treatment for COVID-19; monoclonal antibodies.
【저자키워드】 COVID-19, SARS-CoV-2, monoclonal antibodies, bamlanivimab/etesevimab, casirivimab/imdevimab, early treatment for COVID-19, 【초록키워드】 Treatment, Stratification, vaccination, Trial, Hospitalization, monoclonal antibody, variants of concern, Delta, Intervention, progression, outcome, monoclonal antibodies, Relative risk, variants, bamlanivimab, Probability, Nasopharyngeal swab, Viral, Viral load, Casirivimab, Imdevimab, cycle threshold, etesevimab, Comparative analysis, early treatment, VOCs, Patient, Model, Effectiveness, Factors, death, Ct value, Logistic regression, Alpha, outpatients, PCR test, allocation, Observational data, mAbs, mAb, Evidence, Outpatient, Combination, RT-PCR test, Analysis, Mild-to-moderate, not used, reduction, Factor, Primary outcome, two groups, reduced risk, subject, high viral load, enrolment, ANCOVA, risk reduction, Modification, virological response, negative RT-PCR, Cox model, viral load reduction, was measured, was used, occurred, carried, evaluated, adjusted, were used, determine, in viral, two group, baseline, 【제목키워드】 target,