In Reply We thank Drs Mathew and Feldmann for their comments
on the results of ACTIV-1

Bozzette, Samuel A.

LaVange, Lisa

Powderly, William G.

English

Carolina Digital Repository

In Reply We thank Drs Mathew and Feldmann for their com-ments on the results of ACTIV-1.1 We agree that mortality is avery important clinical outcome, but designing a trial such asACTIV-1 to have sufficient power to detect an effect on mor-tality was challenging in June 2020, when data on clinicaloutcomes of severe COVID-19 were in flux. Indeed, thedesign of ACTIV-1 was heavily influenced by the results ofACTT-1,2 the initial placebo-controlled trial of remdesivir,which showed evidence of improved time to recovery but notimproved mortality.We need to be cautious in interpretation given that theprimary outcome did not reach the prespecified level ofstatistical significance, and, with regard to the outcome ofmortality, we cannot exclude the possibility of a type I error(ie, rejecting the null hypothesis when it is actually true—a“false-positive” result). However, we note the clear differ-ences in all prespecified secondary outcomes, including28-day mortality and clinical status at 14 days. We believe thetotality of the evidence supports a conclusion of possibleclinical benefit for both infliximab and abatacept, and thatconclusion is consistent with trials of other immunomodula-tors (baricitinib and IL-6 inhibitors).3 In summary, we believethat both infliximab and abatacept are reasonable options forclinical use in patients hospitalized with COVID-19.William G. Powderly, MDLisa LaVange, PhDSamuel A. Bozzette, MD, PhDAuthor Affiliations: Division of Infectious Diseases, Washington University inSt Louis, St Louis, Missouri (Powderly); Gillings School of Public Health,University of North Carolina, Chapel Hill (LaVange); National Center forAdvancing Translational Sciences, Bethesda, Maryland (Bozzette).Corresponding Author: William G. Powderly, MD, Division of InfectiousDiseases, Department of Medicine, Washington University School of Medicine,St Louis, MO 63110 (wpowderly@wustl.edu).Conflict of Interest Disclosures: Dr Powderly reported receiving grants fromthe National Center for Advancing Translational Sciences (NCATS) during theconduct of the study and personal fees from Merck Laboratories. Dr LaVangereported receiving grants from NCATS during the conduct of the study.Dr Bozzette reported receiving salary from the National Institutes of Healthduring the conduct of the study.1. O’Halloran JA, Ko ER, Anstrom KJ, et al; ACTIV-1 IM Study Group Members.Abatacept, cenicriviroc, or infliximab for treatment of adults hospitalized withCOVID-19 pneumonia: a randomized clinical trial. JAMA. 2023;330(4):328-339.doi:10.1001/jama.2023.110432. Beigel JH, Tomashek KM, Dodd LE, et al; ACTT-1 Study Group Members.Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa20077643. COVID-19 Treatment Guidelines Panel, National Institutes of Health.Coronavirus disease 2019 (COVID-19) treatment guidelines. AccessedSeptember 10, 2023. https://www.covid19treatmentguidelines.nih.gov/

Treatment of Adults Hospitalized With COVID-19 Pneumonia—Reply

http://cdr.lib.unc.edu/downloads/47429p905

Treatment of Adults Hospitalized With COVID-19 Pneumonia—Reply

Abstract

Similar works

Full text

Available Versions

Carolina Digital Repository