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

• Type of Material: Article
• Authors: Aneesh Mehta, Emory University; Jonathan Fintzi, National Institute of Allergy and Infectious Diseases, Rockville; Tyler Bonnett, Frederick National Laboratory for Cancer Research; Pablo Tebas, University of Pennsylvania; Vincent Marconi, Emory University; Corri B Levine, University of Texas Medical Branch; Hana M El Sahly, Baylor College of Medicine; Susan LF McLellan, University of Texas Medical Branch; Constance A Benson, University of California San Diego; Christina Rostad, Emory University; Anuradha Ganesan, Uniformed Services University of the Health Sciences; Nikhil Huprikar, Uniformed Services University of the Health Sciences; Maria G Frank, University of Colorado; Richard A Mularski, Kaiser Permanente Northwest; Robert L Atmar, Baylor College of Medicine; Pauline K Park, University of Michigan; William R Short, University of Pennsylvania; John H Beigel, National Institute of Allergy and Infectious Diseases, Rockville; Daniel A Sweeney, University of California San Diego
• Language: English
• Date: 2022-07-04
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: 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.
• Final Published Version (URL): http://dx.doi.org/10.1093/ofid/ofac219
• Title of Journal or Parent Work: OPEN FORUM INFECTIOUS DISEASES
• Volume: 9
• Issue: 7
• Start Page: ofac219
• End Page: ofac219
• Grant/Funding Information: This trial has been supported in part by the NIAID of the NIH (M1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, UM169432, and UM1AI148689) and by the NIH Stimulating Access to Research in Residency grant (grant number 5R38AI140299-02).; The ACTT-2 trial was sponsored and primarily funded by the National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, Maryland. This trial has been funded in part with federal funds from the NIAID and the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program.; The trial has also been funded in part by the governments of Japan, Mexico, Denmark, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC_UU_12023/23). V.C.M. received support from the Emory CFAR (grant number P30AI050409). Collaborating investigators involved with collection of data during the ACTT-2 trial are noted in the Supplementary Data.; This analysis used data from the Adaptive Covid-19 Treatment Trial (ACTT-2) trial (DOI: 10.1056/NEJMoa2031994)
• Keywords: Infectious Diseases; Microbiology; Immunology; COVID-19 therapy; MODEL; multistate models; critical care; clinical progression; therapeutics; STRAIN; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Biology, Biostatistics

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.