Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
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 Mendívil-Tuchía de Tai, Akram Khan, Alfredo J Mena Lora, Matthias Salathé, Gerardo Capo, Daniel González, Thomas F. Patterson, Christopher Palma, Horacio Ariza, Maria Patelli Juliani Souza Lima, John Blamoun, Esteban C. Nannini, Eduardo Sprinz, Analía Mykietiuk, Radica Z. Alicic, Adriana M. Rauseo, Cameron R. Wolfe, Britta Witting, Jennifer Wang, Luis Parra-Rodriguez, Tatyana Der, Kate Willsey, Jun Wen, A Silverstein, Sean M. O’Brien, Hussein R. Al‐Khalidi, Michael A. Maldonado, Richard Melsheimer, William Ferguson, Steven E. McNulty, Pearl Zakroysky, Susan Halabi, Daniel K. Benjamin, Sandra Butler, Jane C. Atkinson, Stacey J. Adam, Soju Chang, Lisa M. LaVange, Michael A. Proschan, Samuel A. Bozzette, William G. Powderly, ACTIV-1 IM Study Group Members, Mihir Patel, Arun J. Sanyal, Jason Green, Huimin Wu, Benjamin P. Linas, Philip Grant, Vivek Iyer, Otto O. Yang, Bindu Balani, Sam Parnia, Ryan K Dare, Caryn G. Morse, Estelle S. Harris, Glenn Wortmann, Nicholas S. Hill, Shama Patel, Julia Garcia‐Diaz, Suman Thapamager, Megan Devine, Christine M. Bojanowski, Barry Meisenberg, Gailen D. Marshall, Dima Dandachi, Arick P. Sabin, Anthony Breemo, Suman Sinha, Christopher H. Goss, Rebecca Reece, Arlette Aouad, Seth Glassman, Peter E. Morris, Bela Patel, Fatimah Bello, Juliana Cardozo Fernandes, Oscar Carbajal, L Ravera, Mozar Castro, Miguel Villegas-Chiroque, Fernando Riera, A. Casado Camacho, Claudio Stadnik, Jorge Gave, Rodrigo Biondi, Ronal Gamarra Velarde, José Cerbino Neto, J. Ditondo, Marcelo Losso
Abstract
Importance: Immune dysregulation contributes to poorer outcomes in COVID-19. Objective: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. Design, Setting, and Participants: Randomized, 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. Interventions: Single 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 Measures: The 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. Results: Of 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 Relevance: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04593940.