Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial.

Autor:	O'Brien MP; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Forleo-Neto E; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Sarkar N; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Isa F; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Hou P; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Chan KC; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Musser BJ; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Bar KJ; Department of Medicine, University of Pennsylvania, Philadelphia.; Department of Microbiology, University of Pennsylvania, Philadelphia., Barnabas RV; Department of Global Health, University of Washington, Seattle.; Division of Allergy and Infectious Diseases, University of Washington, Seattle.; Department of Epidemiology, University of Washington, Seattle.; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington., Barouch DH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts., Cohen MS; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill., Hurt CB; Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill., Burwen DR; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland., Marovich MA; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland., Brown ER; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.; Department of Biostatistics, University of Washington, Seattle., Heirman I; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Davis JD; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Turner KC; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Ramesh D; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Mahmood A; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Hooper AT; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Hamilton JD; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Kim Y; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Purcell LA; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Baum A; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Kyratsous CA; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Krainson J; Clinical Trials of Florida LLC, Miami., Perez-Perez R; Medical Research of Westchester, Miami, Florida., Mohseni R; Catalina Research Institute LLC, Montclair, California., Kowal B; Regeneron Pharmaceuticals Inc, Tarrytown, New York., DiCioccio AT; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Geba GP; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Stahl N; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Lipsich L; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Braunstein N; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Herman G; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Yancopoulos GD; Regeneron Pharmaceuticals Inc, Tarrytown, New York., Weinreich DM; Regeneron Pharmaceuticals Inc, Tarrytown, New York.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2022 Feb 01; Vol. 327 (5), pp. 432-441.
DOI:	10.1001/jama.2021.24939
Abstrakt:	Importance: Easy-to-administer anti-SARS-CoV-2 treatments may be used to prevent progression from asymptomatic infection to symptomatic disease and to reduce viral carriage. Objective: To evaluate the effect of combination subcutaneous casirivimab and imdevimab on progression from early asymptomatic SARS-CoV-2 infection to symptomatic COVID-19. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 trial of close household contacts of a SARS-CoV-2-infected index case at 112 sites in the US, Romania, and Moldova enrolled July 13, 2020-January 28, 2021; follow-up ended March 11, 2021. Asymptomatic individuals (aged ≥12 years) were eligible if identified within 96 hours of index case positive test collection. Results from 314 individuals positive on SARS-CoV-2 reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) testing are reported. Interventions: Individuals were randomized 1:1 to receive 1 dose of subcutaneous casirivimab and imdevimab, 1200 mg (600 mg of each; n = 158), or placebo (n = 156). Main Outcomes and Measures: The primary end point was the proportion of seronegative participants who developed symptomatic COVID-19 during the 28-day efficacy assessment period. The key secondary efficacy end points were the number of weeks of symptomatic SARS-CoV-2 infection and the number of weeks of high viral load (>4 log10 copies/mL). Results: Among 314 randomized participants (mean age, 41.0 years; 51.6% women), 310 (99.7%) completed the efficacy assessment period; 204 were asymptomatic and seronegative at baseline and included in the primary efficacy analysis. Subcutaneous casirivimab and imdevimab, 1200 mg, significantly prevented progression to symptomatic disease (29/100 [29.0%] vs 44/104 [42.3%] with placebo; odds ratio, 0.54 [95% CI, 0.30-0.97]; P = .04; absolute risk difference, -13.3% [95% CI, -26.3% to -0.3%]). Casirivimab and imdevimab reduced the number of symptomatic weeks per 1000 participants (895.7 weeks vs 1637.4 weeks with placebo; P = .03), an approximately 5.6-day reduction in symptom duration per symptomatic participant. Treatment with casirivimab and imdevimab also reduced the number of high viral load weeks per 1000 participants (489.8 weeks vs 811.9 weeks with placebo; P = .001). The proportion of participants receiving casirivimab and imdevimab who had 1 or more treatment-emergent adverse event was 33.5% vs 48.1% for placebo, including events related (25.8% vs 39.7%) or not related (11.0% vs 16.0%) to COVID-19. Conclusions and Relevance: Among asymptomatic SARS-CoV-2 RT-qPCR-positive individuals living with an infected household contact, treatment with subcutaneous casirivimab and imdevimab antibody combination vs placebo significantly reduced the incidence of symptomatic COVID-19 over 28 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04452318.
Databáze:	MEDLINE
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