Impact of Antibody Cocktail Therapy Combined with Casirivimab and Imdevimab on Clinical Outcome for Covid-19 patients in A Real-Life Setting: A Single Institute Analysis
et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.01.067, Nov 2021 (preprint)
18th treatment shown to reduce risk in
March 2021, now with p = 0.000095 from 34 studies, recognized in 52 countries.
Efficacy is variant dependent.
No treatment is 100% effective. Protocols
combine treatments.
6,200+ studies for
200+ treatments. c19early.org
|
Retrospective 55 patients in Japan treated a median of 3 days from symptom onset with casirivimab/imdevimab, and 53 control patients, showing lower risk of further treatment including oxygen or antivirals.
Efficacy is variant dependent. In Vitro research suggests a lack of efficacy for many omicron variants1-7.
Standard of Care (SOC) for COVID-19 in the study country,
Japan, is very poor with very low average efficacy for approved treatments8.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
|
risk of further treatment including oxygen or antivirals, 57.6% lower, RR 0.42, p = 0.049, treatment 13 of 55 (23.6%), control 22 of 53 (41.5%), NNT 5.6, adjusted per study, odds ratio converted to relative risk, multivariable.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
1.
Liu et al., Striking Antibody Evasion Manifested by the Omicron Variant of SARS-CoV-2, bioRxiv, doi:10.1101/2021.12.14.472719.
2.
Sheward et al., Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron), bioRxiv, doi:10.1101/2021.12.19.473354.
3.
VanBlargan et al., An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies, bioRxiv, doi:10.1101/2021.12.15.472828.
4.
Tatham et al., Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice, bioRxiv, doi:10.1101/2022.01.23.477397.
5.
Pochtovyi et al., In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, Vaccines, doi:10.3390/vaccines11101533.
6.
Haars et al., Prevalence of SARS-CoV-2 Omicron Sublineages and Spike Protein Mutations Conferring Resistance against Monoclonal Antibodies in a Swedish Cohort during 2022–2023, Microorganisms, doi:10.3390/microorganisms11102417.
Kakinoki et al., 4 Nov 2021, retrospective, Japan, peer-reviewed, 16 authors, average treatment delay 3.0 days.
Impact of Antibody Cocktail Therapy Combined with Casirivimab and Imdevimab on Clinical Outcome for patients with COVID-19 in A Real-Life Setting: A Single Institute Analysis
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.01.067
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AUTHOR CONTRIBUTIONS: Design of research studies: YK and KY. Data acquisition: TK, KY, GA, and NS. Data analysis: YK and KY. Writing the manuscript: YK. All authors worked hard to take care of patients with Covid-19.
References
Baum, Fulton, Wloga, Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies, Science
Copin, Baum, Wloga, The monoclonal antibody combination REGEN-COV protects against SARS-C0V-2 mutational escape in preclinical and human studies, Cell
Hansen, Baum, Pascal, Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail, Science
Ikemura, Hoshino, Higuchi, SARS-CoV-2 Omicron variant escapes neutralization by vaccinated and convalescent sera and therapeutic monoclonal antibodies, doi:10.1101/2021.12.13.21267761
Kanda, Investigation of the freely-available easy-to-use software"EZR" (Easy R) for medical statistics, Bone Marrow Transplant, doi:10.1038/bmt.2012.244
Wang, Nair, Liu, Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7, Nature
Weinreich, Sivapalasingam, Norton, REGEN-COV antibody cocktail clinical outcomes study in Covid-19 outpatients, doi:10.1101/2021.05.19.21257469v2
Weinreich, Sivapalasingam, Norton, REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19, N Engl J Med
Welfare, Brien, Forleo-Neto, Musser, Approval for Ronapreve TM (casirivimab and imdevimab) for the treatment of patients with mild to moderate Covid-19, N Engl J Med
Wilhelm, Widera, Grikscheit, Reduced neutralization of SARS-CoV-2 omicron variant by vaccine sera and monoclonal antibodies, doi:10.1101/2021.12.07.21267432
Wu, Zhao, Yu, A new coronavirus associated with human respiratory disease in China, Nature
Zhu, Zhang, Wang, A novel coronavirus from patients with pneumonia in China, 2019, N Engl J Med
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