Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
Creators: name: Butler, Sandra
name: Der, Tatyana
name: Nunez, Patricia Segura
name: Salathe, Matthias
name: Nannini, Esteban C.
name: Zakroysky, Pearl
name: Powderly, William G.
name: McNulty, Steven E.
name: Parra-Rodriguez, Luis
name: Proschan, Michael
name: Smith, P. Brian
name: McCarthy, Matthew W.
name: Lora, Alfredo J. Mena
name: Lima, Maria Patelli
name: Ferguson, William G.
name: Anstrom, Kevin J.
name: Rauseo, Adriana M.
name: O’Brien, Sean M.
name: Benjamin, Daniel K.
name: Wen, Jun
name: Maillo, Martin
name: Chang, Soju
name: Silverstein, Adam
name: Mykietiuk, Analia
name: Alicic, Radica
name: Palma, Christopher
name: Panettieri, Reynold A.
name: Atkinson, Jane C.
name: Gonzalez, Cynthia
name: Sprinz, Eduardo
name: Halabi, Susan
name: Kedar, Eyal
name: Gonzalez, Daniel Rodríguez
name: Blamoun, John
name: Khan, Akram
name: Bozzette, Samuel A.
name: Ko, Emily R.
name: Melsheimer, Richard
name: Capo, Gerardo
name: Wang, Jennifer P.
name: Al-Khalidi, Hussein R.
name: Maldonado, Michael A.
name: Wolfe, Cameron R.
name: Witting, Britta
name: ACTIV-1 IM Study Group Members
name: de Tai, Sabina Mendivil-Tuchia
name: Lachiewicz, Anne M.
name: Ariza, Horacio
name: LaVange, Lisa
name: O’Halloran, Jane A.
name: Willsey, Kate
name: Adam, Stacey J.
name: Patterson, Thomas F.
Publisher: name: American Medical Association (AMA)
Year: 2023

description: <p>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&thinsp;=&thinsp;.09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P&thinsp;=&thinsp;.94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P&thinsp;=&thinsp;.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.</p>