TY - JOUR
T1 - Casirivimab and Imdevimab for the Treatment of Hospitalized Patients with COVID-19
AU - the COVID-19 Phase 2/3 Hospitalized Trial Team
AU - Somersan-Karakaya, Selin
AU - Mylonakis, Eleftherios
AU - Menon, Vidya P.
AU - Wells, Jason C.
AU - Ali, Shazia
AU - Sivapalasingam, Sumathi
AU - Sun, Yiping
AU - Bhore, Rafia
AU - Mei, Jingning
AU - Miller, Jutta
AU - Cupelli, Lisa
AU - Forleo-Neto, Eduardo
AU - Hooper, Andrea T.
AU - Hamilton, Jennifer D.
AU - Pan, Cynthia
AU - Pham, Viet
AU - Zhao, Yuming
AU - Hosain, Romana
AU - Mahmood, Adnan
AU - Davis, John D.
AU - Turner, Kenneth C.
AU - Kim, Yunji
AU - Cook, Amanda
AU - Kowal, Bari
AU - Soo, Yuhwen
AU - DiCioccio, A. Thomas
AU - Geba, Gregory P.
AU - Stahl, Neil
AU - Lipsich, Leah
AU - Braunstein, Ned
AU - Herman, Gary A.
AU - Yancopoulos, George D.
AU - Weinreich, David M.
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).METHODS: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus.RESULTS: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted.CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.CLINICAL TRIALS REGISTRATION: NCT04426695.
AB - BACKGROUND: The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).METHODS: In this phase 1/2/3, double-blind, placebo-controlled trial conducted prior to widespread circulation of Delta and Omicron, hospitalized COVID-19 patients were randomized (1:1:1) to 2.4 g or 8.0 g CAS + IMD or placebo, and characterized at baseline for viral load and SARS-CoV-2 serostatus.RESULTS: In total, 1336 patients on low-flow or no supplemental (low-flow/no) oxygen were treated. The primary endpoint was met in seronegative patients, the least-squares mean difference (CAS + IMD versus placebo) for time-weighted average change from baseline in viral load through day 7 was -0.28 log10 copies/mL (95% confidence interval [CI], -.51 to -.05; P = .0172). The primary clinical analysis of death or mechanical ventilation from day 6 to 29 in patients with high viral load had a strong positive trend but did not reach significance. CAS + IMD numerically reduced all-cause mortality in seronegative patients through day 29 (relative risk reduction, 55.6%; 95% CI, 24.2%-74.0%). No safety concerns were noted.CONCLUSIONS: In hospitalized COVID-19 patients on low-flow/no oxygen, CAS + IMD reduced viral load and likely improves clinical outcomes in the overall population, with the benefit driven by seronegative patients, and no harm observed in seropositive patients.CLINICAL TRIALS REGISTRATION: NCT04426695.
KW - COVID-19
KW - SARS-CoV-2
KW - coronavirus
KW - hospitalized
KW - monoclonal antibody
KW - COVID-19 Drug Treatment
KW - Double-Blind Method
KW - Humans
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U2 - 10.1093/infdis/jiac320
DO - 10.1093/infdis/jiac320
M3 - Article
C2 - 35895508
AN - SCOPUS:85138738489
SN - 0022-1899
VL - 227
SP - 23
EP - 34
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -