• Jane A O'Halloran, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W McCarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, Anne M Lachiewicz, Cynthia Gonzalez, P Brian Smith, Sabina Mendivil-Tuchia de Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathe, Gerardo Capo, Daniel Rodríguez Gonzalez, Thomas F Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Lima, John Blamoun, Esteban C Nannini, Eduardo Sprinz, Analia Mykietiuk, Radica Alicic, Adriana M Rauseo, Cameron R Wolfe, Britta Witting, Jennifer P Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, Adam Silverstein, Sean M O'Brien, Hussein R Al-Khalidi, Michael A Maldonado, Richard Melsheimer, William G Ferguson, Steven E McNulty, Pearl Zakroysky, Susan Halabi, Daniel K Benjamin, Sandra Butler, Jane C Atkinson, Stacey J Adam, Soju Chang, Lisa LaVange, Michael Proschan, Samuel A Bozzette, William G Powderly, and ACTIV-1 IM Study Group Members.
• Washington University St Louis, St Louis, Missouri.
• JAMA. 2023 Jul 25; 330 (4): 328339328-339.

ImportanceImmune dysregulation contributes to poorer outcomes in COVID-19.ObjectiveTo investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.Design, Setting, And ParticipantsRandomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021.InterventionsSingle infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day).Main Outcomes And MeasuresThe primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale.ResultsOf the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies.Conclusions And RelevanceTime to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT04593940.

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