Frontiers in Immunology (Apr 2022)

Emulation of a Target Trial From Observational Data to Compare Effectiveness of Casirivimab/Imdevimab and Bamlanivimab/Etesevimab for Early Treatment of Non-Hospitalized Patients With COVID-19

  • Valentina Mazzotta,
  • Alessandro Cozzi-Lepri,
  • Francesca Colavita,
  • Simone Lanini,
  • Silvia Rosati,
  • Eleonora Lalle,
  • Ilaria Mastrorosa,
  • Claudia Cimaglia,
  • Alessandra Vergori,
  • Nazario Bevilacqua,
  • Daniele Lapa,
  • Andrea Mariano,
  • Aurora Bettini,
  • Chiara Agrati,
  • Pierluca Piselli,
  • Enrico Girardi,
  • Concetta Castilletti,
  • Anna Rosa Garbuglia,
  • Francesco Vaia,
  • Emanuele Nicastri,
  • Andrea Antinori

DOI
https://doi.org/10.3389/fimmu.2022.868020
Journal volume & issue
Vol. 13

Abstract

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ObjectivesComparative 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.MethodsAllocation 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.ResultsCOVID19-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.ConclusionsIn 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.

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