Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection
J Ryan Bariola, PharmD Erin K Mccreary, MD Richard J Wadas, PhD Kevin E Kip, MD Oscar C Marroquin, MSN Tami Minnier, BS Stephen Koscumb, BS Kevin Collins, MD Mark Schmidhofer, Judith A Shovel, MT Mary Kay Wisniewski, Colleen Sullivan, MD Donald M Yealy, MD MPH David A Nace, MD MPH David T Huang, MD Ghady Haidar, Tina Khadem, MS Kelsey Linstrum, MD MSc Christopher W Seymour, MS Stephanie K Montgomery, MD MPH FRCP Derek C Angus, MD SM Graham M Snyder
doi:10.1101/2021.03.25.21254322
Background: Monoclonal antibody (mAb) treatment may prevent complications of COVID-19. We sought to quantify the impact of bamlanivimab monotherapy on hospitalizations and mortality, as well as Emergency Department (ED) visits without hospitalization, among outpatients at high risk of COVID-19 complications.
Methods: We compared patients receiving mAb to patients who met criteria but did not receive mAb from December 2020 through March 2021. The study population selection used propensity scores to match 1:1 by likelihood to receive mAb. The primary outcome was hospitalization or all-cause mortality within 28 days; the secondary outcome was hospitalization or ED visit without hospitalization within 28 days. Odds ratios (OR) calculation used logistic regression modeling including propensity score and mAb receipt predictors.
Results: The study population included 234 patients receiving mAb and 234 matched comparator patients not receiving mAb. Patients receiving mAb were less likely to experience hospitalization or mortality (OR 0.31, 95% confidence interval [95%CI] 0.17-0.56, p=0.00001) and hospitalization or ED visit without hospitalization (OR 0.50, 95%CI 0.43-0.83, p=0.007). The impact of mAb was more pronounced in prevention of hospitalization (among all age groups, OR 0.35, 95%CI 0.19-0.66, p=0.001) than mortality or ED visit without hospitalization, and most strongly associated with patients age 65 years and older (primary outcome OR 0.28, 95%CI 0.14-0.56, p=0.0003).
Conclusions : Bamlanivimab monotherapy was associated with reduction in the composite outcome of hospitalizations and mortality in patients with mild-moderate COVID-19. The benefit may be strongest in preventing hospitalization in patients ages 65 years or older. . CoV016; Eli Lilly), casirivimab 1,200mg (REGN10933; Regeneron), imdevimab 1,200mg (REGN10987). Several clinical trials currently evaluate mAbs for prevention or treatment of COVID-19; however, real-world data are limited, and the role of mAbs for patients with COVID-19 remains controversial. 3, 5 Use of mAb therapy is low in the United States despite widespread drug availability due to lack of robust efficacy data, operational challenges with outpatient infusions, and patient access issues. 6 Our health system established a mAb program in November 2020 to decrease COVID-19-related complications for patients with mild-moderate illness and expand access to care for underserved patients with COVID-19. Initially, only bamlanivimab monotherapy was available; our evaluation and distribution process has been described elsewhere. 7 This study quantifies the impact of bamlanivimab monotherapy on hospitalizations, mortality, and Emergency Department (ED) visits among outpatients at high risk of progressing to severe COVID-19. We also explored whether patient age, body mass index, and timing of infusions relative to initial diagnosis had any association with response to therapy.
METHODS
Study Setting .
Conflict of Interest Disclosure: None of the authors received any payments or influence from a third-party source for the work presented, and none report any potential conflicts of interest.
SUPPLEMENTAL MATERIALS
References
Ault, Rollout of COVID Monoclonal Antibodies Lacked Unified Plan: Expert Panel
Austin, An Introduction to Propensity Score Methods for Reducing the Effects of Confounding in Observational Studies, Multivariate Behav Res. May,
doi:10.1080/00273171.2011.568786
Bajaj, Gadi, Spihlman, Wu, Choi et al., Aging, Immunity, and COVID-19: How Age Influences the Host Immune Response to Coronavirus Infections?, Front Physiol,
doi:10.3389/fphys.2020.571416
Bariola, Mccreary, Khadem, Snyder, Wadas et al., Establishing a Distribution Network for COVID-19 Monoclonal Antibody Therapy Across a Large Health System During a Global Pandemic, Open Forum Infect Dis
Benchimol, Smeeth, Guttmann, The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement, PLoS Med,
doi:10.1371/journal.pmed.1001885
Chen, Nirula, Heller, SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2029849
Cohen1, Nirula2, Mulligan3, Novak4, Marovich5 et al., ). Bamlanivimab prevents COVID-19 morbidity and mortality in nursinghome setting
Gottlieb, Nirula, Chen, Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial, Jama,
doi:10.1001/jama.2021.0202
Jones, Brown-Augsburger, Corbett, LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection, bioRxiv,
doi:10.1101/2020.09.30.318972
Lim, Subramaniam, Reddy, Case Fatality Rates for Patients with COVID-19 Requiring Invasive Mechanical Ventilation. A Meta-analysis, Am J Respir Crit Care Med. Jan,
doi:10.1164/rccm.202006-2405OC
Reitz, Marroquin, Zenati, Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes, JAMA Surg. Jun,
doi:10.1001/jamasurg.2020.0416
Richardson, Hirsch, Narasimhan, Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area, JAMA,
doi:10.1001/jama.2020.6775
Rosenbaum, Db, The central role of the propensity score in observational studies for causal effects, Biometrika,
doi:10.1093/biomet/70.1.41
Tartof, Qian, Hong, Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization, Ann Intern Med. Nov,
doi:10.7326/m20-3742
Webb, Buckel, Vento, Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Ambulatory Patients with Early COVID-19,
doi:10.1101/2021.03.15.21253646
Weinreich, Sivapalasingam, Norton, REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19, N Engl J Med,
doi:10.1056/NEJMoa2035002