Real World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients
MD, MHSc Neil R Aggarwal, MS Laurel E Beaty, MD Tellen D Bennett, PhD, MS Nichole E Carlson, MD d ; Christopher B Davis, PhD Bethany M Kwan, BS David A Mayer, PhD Toan C Ong, MS Seth Russell, RN g ; Jeffrey Steele, PhD Adane F Wogu, MD, MPH Matthew K Wynia, MD Richard D Zane, MD, MPH Adit A Ginde
doi:10.1101/2022.04.03.22273360
Background: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic COVID-19 patients, is effective against the SARS-CoV-2 Delta variant to prevent progression to severe disease and mortality. Methods: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from October 1 st 2021 -December 11 th 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. We used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. Results: Of 10,036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1,563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% versus 5.7%; adjusted OR 0.37, 95% CI 0.19-0.66) and an 89% decrease in the odds of allcause 28-day mortality (raw rate 0% versus 1.0%; adjusted OR 0.11, 95% CI 0.0-0.79), and may reduce respiratory disease severity among those hospitalized.
Conclusion: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.
References
Angus, Optimizing the Trade-off Between Learning and Doing in a Pandemic, JAMA
Austin, An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies, Multivariate Behav Res
Austin, Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples, Stat Med
Bennett, Moffitt, Hajagos, Clinical Characterization and Prediction of Clinical Severity of SARS-CoV-2 Infection Among US Adults Using Data From the US National COVID Cohort Collaborative, JAMA Netw Open
Bernstein, Biden Administration moves to stave off shortages of monoclonal antibodies, Accessed
Cameroni, Saliba, Bowen, Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift, bioRxiv
Cavazzoni, Coronavirus (COVID-19) Update: FDA Limits Use of Certain 9. ISPOR. About real-world evidence
Dougan, Nirula, Azizad, Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19, N Engl J Med
Gupta, Gonzalez-Rojas, Juarez, Effect of Sotrovimab on Hospitalization or Death Among High-risk Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA
Heinze, Schemper, A solution to the problem of separation in logistic regression, Stat Med
Heinze, logistf: Firth's Bias-Reduced Logistic Regression, R package version
Ho, King, Stuart, Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference, Political Analysis
Lynch, Caplan, Furlong, Bateman-House, Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?, Am J Bioeth
Puhr, Heinze, Nold, Lusa, Geroldinger, Firth's logistic regression with rare events: accurate effect estimates and predictions?, Stat Med
Team, a language and environment for statistical computing
Vanblargan, Errico, Halfmann, An infectious SARS-CoV-2 B
Weinreich, Sivapalasingam, Norton, REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19, N Engl J Med
Wynia, Beaty, Bennett, Real World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients, medRxiv
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>It is not known whether sotrovimab, a neutralizing monoclonal '
'antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) '
'patients, is also effective in preventing the progression of severe disease and mortality '
'following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant '
'infection.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>In an observational cohort study of nonhospitalized adult patients '
'with SARS-CoV-2 infection, 1 October 2021–11 December 2021, using electronic health records '
'from a statewide health system plus state-level vaccine and mortality data, we used '
'propensity matching to select 3 patients not receiving mAbs for each patient who received '
'outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary '
'outcomes included mortality and severity of hospitalization.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>Of 10 036 patients with SARS-CoV-2 infection, 522 receiving '
'sotrovimab were matched to 1563 not receiving mAbs. Compared to mAb-untreated patients, '
'sotrovimab treatment was associated with a 63% decrease in the odds of all-cause '
'hospitalization (raw rate 2.1% vs 5.7%; adjusted odds ratio [aOR], 0.37; 95% confidence '
'interval [CI], .19–.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw '
'rate 0% vs 1.0%; aOR, 0.11; 95% CI, .0–.79), and may reduce respiratory disease severity '
'among those hospitalized.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
' <jats:p>Real-world evidence demonstrated sotrovimab effectiveness in '
'reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the '
'Delta variant phase.</jats:p>\n'
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'development and access inform approaches to non-pandemic diseases?',
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'with emergence of the Delta variant',
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'confounding in observational studies',
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'covariates between treatment groups in propensity-score matched samples',
'volume': '28',
'author': 'Austin',
'year': '2009',
'journal-title': 'Stat Med'},
{'key': '2023052402435640300_jiac206-B19', 'author': 'National Institute of Health.'},
{'key': '2023052402435640300_jiac206-B20', 'author': 'Heinz', 'year': '2020'},
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'year': '2002',
'journal-title': 'Stat Med'},
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'and predictions?',
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'year': '2017',
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'volume-title': 'R: a language and environment for statistical computing',
'author': 'R Core Team',
'year': '2020'},
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'article-title': 'Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic '
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'article-title': 'Antibody evasion properties of SARS-CoV-2 Omicron sublineages',
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'author': 'Iketani',
'year': '2022',
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'volume': '386',
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