Casirivimab and Imdevimab for the Treatment of Hospitalized Patients With COVID-19
MD Selin Somersan-Karakaya, MD Eleftherios Mylonakis, MD Vidya P Menon, MD Jason C Wells, PharmD Shazia Ali, MD Sumathi Sivapalasingam, PhD Yiping Sun, PhD Rafia Bhore, PhD Jingning Mei, BS, RN Jutta Miller, PhD Lisa Cupelli, MD Eduardo Forleo-Neto, PhD Andrea T Hooper, PhD Jennifer D Hamilton, Cynthia Pan, BS Viet Pham, MS Yuming Zhao, MD, MPH Romana Hosain, MD Adnan Mahmood, PhD John D Davis, PhD Kenneth C Turner, PharmD Yunji Kim, BS, Dip.Reg Amanda Cook, Aff, MS Bari Kowal, PhD Yuhwen Soo, PhD A Thomas Dicioccio, MD Gregory P Geba, Dr Ph, PhD Neil Stahl, PhD Leah Lipsich, MD Ned Braunstein, MD Gary A Herman, MD, PhD George D Yancopoulos, MD David M Weinreich
doi:10.1093/infdis/jiac320/6650790
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 I/II/III, 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: 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 log 10 copies/mL (95% CI, -0.51 to -0.05; P=.0172). The primary clinical analysis of death or mechanical ventilation (death/MV) from day 6-29 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.
Notes Forest plot shows relative risk and relative risk reduction with 95% CIs for CAS+IMD combined dose analysis (2.4 g and 8.0 g) versus placebo. Parameters examined include death within 28 days, discharge alive from hospital from days 1 to 29, and death or mechanical ventilation from days 1 to 29. For all populations, the mFAS was comprised of patients who tested positive for SARS-CoV-2 at baseline. Populations analyzed include patients who tested negative for all SARS-CoV-2 antibodies at baseline (seronegative mFAS), patients who tested positive for any SARS-CoV-2 antibody at baseline (seropositive mFAS), those with borderline, inconclusive or missing baseline serology (other), and the overall population regardless of serostatus (overall mFAS). For the proportion of death within 28 days and the proportion of death or mechanical ventilation with 28 days, the lower bounds of the CI of the relative risk reduction were -342.0% and -241.0%, respectively, which are presented as "NA" in the figure . Abbreviations: CAS+IMD, casirivimab and imdevimab; CI, confidence interval; mFAS, modified full analysis set; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
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DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>The open-label RECOVERY study reported improved survival in hospitalized, SARS-CoV-2 seronegative patients treated with casirivimab and imdevimab (CAS + IMD).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>In this phase I/II/III, 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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>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% CI, –0.51 to –0.05; P = .0172). The primary clinical analysis of death or mechanical ventilation (death/MV) from day 6–29 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.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>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.</jats:p>\n </jats:sec>",
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