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. 2023 Apr 3;6(4):e239694.
doi: 10.1001/jamanetworkopen.2023.9694.

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes

Nalini Ambrose  1 , Alpesh Amin  2   3 , Brian Anderson  1 , Julio Barrera-Oro  4 , Monica Bertagnolli  5 , Francis Campion  1   6 , Daniel Chow  7 , Risa Danan  1 , Lauren D'Arinzo  1 , Ashley Drews  8   9   10 , Karl Erlandson  4 , Kristin Fitzgerald  1 , Melissa Garcia  1 , Fraser W Gaspar  1 , Carlene Gong  11 , George Hanna  12 , Stephen Jones  13 , Bert Lopansri  14   15 , James Musser  16   17   18 , John O'Horo  19 , Steven Piantadosi  20 , Bobbi Pritt  19 , Raymund R Razonable  19 , Seth Roberts  1 , Suzanne Sandmeyer  21   22 , David Stein  1 , Farhaan Vahidy  13   23   24 , Brandon Webb  14   15 , Jennifer Yttri  1
Affiliations

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes

Nalini Ambrose et al. JAMA Netw Open. .

Abstract

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice.

Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes.

Design, setting, and participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome.

Exposure: Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting.

Main outcomes and measures: Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022).

Results: Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%).

Conclusions and relevance: In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Amin reported receiving grants from the University of California, Irvine, during the conduct of the study; grants from Alexion Pharmaceuticals, Blade Therapeutics, Eli Lilly and Company, Fulcrum Therapeutics, Humanigen, the National Institute of Allergy and Infectious Diseases, Novartis, NRx Pharmaceuticals, Octapharma, Pulmotect, PTC Therapeutics, and Takeda Pharmaceuticals; and personal fees from Achogen LaJolla, Alexion Pharmaceuticals, AseptiScope, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly and Company, Ferring Pharmaceuticals, Gilead Sciences, HeartRite, Millennium Pharmaceuticals, Mylan, Nabriva Therapeutics, Novartis, Paratek Pharmaceuticals, Pfizer, Portola Pharmaceuticals, Salix Pharmaceuticals, Seres Therapeutics, Spero Therapeutics, Sprightly Health, Sunovion Pharmaceuticals, and Tetraphase Pharmaceuticals outside the submitted work. Dr Bertagnolli reported receiving personal fees from The MITRE Corporation during the conduct of the study. Dr Chow reported receiving personal fees from Canon Medical Systems outside the submitted work. Dr Drews reported receiving grants from The MITRE Corporation during the conduct of the study and outside the submitted work. Dr Hanna reported receiving personal fees from Abpro Corporation and Merck & Co outside the submitted work. Dr Jones reported receiving personal fees from The MITRE Corporation during the conduct of the study. Dr Lopansri reported receiving personal fees from Seegene outside the submitted work. Dr O’Horo reported receiving grants from The MITRE Corporation during the conduct of the study; grants from nference; and personal fees from Bates College outside the submitted work. Dr Piantadosi reported receiving personal fees from The MITRE Corporation during the conduct of the study and outside the submitted work. Dr Pritt reported receiving funding from The MITRE Corporation during the conduct of the study. Dr Razonable reported receiving grants from Gilead Sciences, Regeneron Pharmaceuticals, and Roche and personal fees from Novartis outside the submitted work. Dr Webb reported receiving grants from Gilead Sciences and Regeneron Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cohort Flow Diagram for Main Analysis and Variant Analysis Using Genomic Sequences
nMAb indicates neutralizing monoclonal antibody.
Figure 2.
Figure 2.. Association of Neutralizing Monoclonal Antibodies (nMAbs) With Adverse Outcomes by Risk Factor
An odds ratio (OR) less than 1 indicates reduced risk, and an OR greater than 1 indicates treatment was associated with an adverse outcome. The 30-day composite outcome comprised hospitalization or death. NA indicates not applicable.
Figure 3.
Figure 3.. Associationof Neutralizing Monoclonal Antibodies With Adverse Outcomes by Variant Epoch, Variant Sequence, and Neutralizing Monoclonal Antibody Product
Odds ratios (ORs) are only shown when at least 100 patients were treated with a neutralizing monoclonal antibody product per variant epoch or sequence. An OR less than 1 indicates reduced risk, and an OR greater than 1 indicates treatment was associated with an adverse outcome. The 30-day composite outcome comprised hospitalization or death. WHO indicates World Health Organization.
See this image and copyright information in PMC

Comment in

References

    1. Chen P, Nirula A, Heller B, et al. ; BLAZE-1 Investigators . SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with COVID-19. N Engl J Med. 2021;384(3):229-237. doi:10.1056/NEJMoa2029849 - DOI - PMC - PubMed
    1. Weinreich DM, Sivapalasingam S, Norton T, et al. ; Trial Investigators . REGEN-COV antibody combination and outcomes in outpatients with COVID-19. N Engl J Med. 2021;385(23):e81. doi:10.1056/NEJMoa2108163 - DOI - PMC - PubMed
    1. Gupta A, Gonzalez-Rojas Y, Juarez E, et al; COMET-ICE Investigators. Early treatment for COVID-19 with SARS-CoV-2 neutralizing antibody sotrovimab. N Engl J Med. 2021;385(21):1941-1950. doi:10.1056/NEJMoa2107934 - DOI - PubMed
    1. Dougan M, Nirula A, Azizad M, et al. ; BLAZE-1 Investigators . Bamlanivimab plus etesevimab in mild or moderate COVID-19. N Engl J Med. 2021;385(15):1382-1392. doi:10.1056/NEJMoa2102685 - DOI - PMC - PubMed
    1. US Food & Drug Administration . Real-world evidence. US Food & Drug Administration. Updated January 31, 2023. Accessed March 2, 2022. https://www.fda.gov/science-research/science-and-research-special-topics...

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