Unraveling the Treatment Effect of Baricitinib on Clinical Progression and Resource Utilization in Hospitalized COVID-19 Patients: Secondary Analysis of the Adaptive COVID-19 Treatment Randomized Trial-2

Jonathan Fintzi; Tyler Bonnett; Pablo Tebas; Vincent C Marconi; Corri B Levine; Hana M El Sahly; Susan L F McLellan; Constance A Benson; Christina A Rostad; Anuradha Ganesan; Nikhil Huprikar; Maria G Frank; Richard A Mularski; Robert L Atmar; Pauline K Park; William R Short; John H Beigel; Aneesh K Mehta; Daniel A Sweeney

doi:10.1093/ofid/ofac219

Unraveling the Treatment Effect of Baricitinib on Clinical Progression and Resource Utilization in Hospitalized COVID-19 Patients: Secondary Analysis of the Adaptive COVID-19 Treatment Randomized Trial-2

Open Forum Infect Dis. 2022 Apr 27;9(7):ofac219. doi: 10.1093/ofid/ofac219. eCollection 2022 Jul.

Authors

Jonathan Fintzi¹, Tyler Bonnett², Pablo Tebas³, Vincent C Marconi⁴, Corri B Levine⁵, Hana M El Sahly⁶, Susan L F McLellan⁵, Constance A Benson⁷, Christina A Rostad⁸, Anuradha Ganesan⁹, Nikhil Huprikar¹⁰, Maria G Frank¹¹, Richard A Mularski¹², Robert L Atmar¹³, Pauline K Park¹⁴, William R Short¹⁵, John H Beigel¹⁶, Aneesh K Mehta¹⁷, Daniel A Sweeney¹⁸

Affiliations

¹ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
² Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
³ Division of Infectious Diseases/Clinical Trials Unit, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
⁴ Emory University School of Medicine and Rollins School of Public Health, Emory Vaccine Center, Atlanta Veterans Affairs Medical Center, Atlanta, Georgia, USA.
⁵ Division of Infectious Disease, Department of Medicine, University of Texas Medical Branch, Galveston, Texas, USA.
⁶ Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
⁷ Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
⁸ Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
⁹ Division of Infectious Disease, Walter Reed National Military Medical Center, Infectious Disease Clinical Research Program, Uniformed Services University of the Health Sciences, Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA.
¹⁰ Division of Pulmonary/Critical Care Medicine, Walter Reed National Military Medical Center, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
¹¹ Department of Medicine, Denver Health Hospital Authority, Associate Professor of Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
¹² The Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA.
¹³ Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
¹⁴ Division of Acute Care Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
¹⁵ Division of Infectious Diseases, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁶ Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
¹⁷ Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
¹⁸ Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Abstract

Background: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies.

Methods: We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment. We estimated the effect of BCT on cumulative incidence of clinical improvement and deterioration using competing risks models. We developed multistate models to estimate the effect of BCT on clinical improvement and deterioration and on utilization of respiratory therapies.

Results: BCT resulted in more linear improvement and lower incidence of clinical deterioration compared with RMT (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95). The benefit was pronounced among participants enrolled on high-flow oxygen or noninvasive positive-pressure ventilation. In this group, BCT sped clinical improvement (HR, 1.21; 95% CI, 0.99 to 1.51) while slowing clinical deterioration (HR, 0.71; 95% CI, 0.48 to 1.02), which reduced the expected days in ordinal score (OS) 6 per 100 patients by 74 days (95% CI, -8 to 154 days) and the expected days in OS 7 per 100 patients by 161 days (95% CI, 46 to 291 days) compared with RMT. BCT did not benefit participants who were mechanically ventilated at enrollment.

Conclusions: Compared with RMT, BCT reduces the clinical burden and utilization of intensive respiratory therapies for patients requiring low-flow oxygen or noninvasive positive-pressure ventilation compared with RMT and may thereby improve care for this patient population.

Keywords: COVID-19 therapy; clinical progression; critical care; multistate models; therapeutics.

Published by Oxford University Press on behalf of Infectious Diseases Society of America. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Abstract

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