TY - JOUR
T1 - Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia
T2 - A Randomized Clinical Trial
AU - ACTIV-1 IM study group members
AU - O'Halloran, Jane A
AU - Ko, Emily R
AU - Anstrom, Kevin J
AU - Kedar, Eyal
AU - McCarthy, Matthew W
AU - Panettieri, Reynold A
AU - Maillo, Martin
AU - Nunez, Patricia Segura
AU - Lachiewicz, Anne M
AU - Gonzalez, Cynthia
AU - Smith, P Brian
AU - de Tai, Sabina Mendivil-Tuchia
AU - Khan, Akram
AU - Lora, Alfredo J Mena
AU - Salathe, Matthias
AU - Capo, Gerardo
AU - Gonzalez, Daniel Rodríguez
AU - Patterson, Thomas F
AU - Palma, Christopher
AU - Ariza, Horacio
AU - Lima, Maria Patelli
AU - Blamoun, John
AU - Nannini, Esteban C
AU - Sprinz, Eduardo
AU - Mykietiuk, Analia
AU - Alicic, Radica
AU - Rauseo, Adriana M
AU - Wolfe, Cameron R
AU - Witting, Britta
AU - Wang, Jennifer P
AU - Parra-Rodriguez, Luis
AU - Der, Tatyana
AU - Willsey, Kate
AU - Wen, Jun
AU - Silverstein, Adam
AU - O'Brien, Sean M
AU - Al-Khalidi, Hussein R
AU - Maldonado, Michael A
AU - Melsheimer, Richard
AU - Ferguson, William G
AU - McNulty, Steven E
AU - Zakroysky, Pearl
AU - Halabi, Susan
AU - Benjamin, Daniel K
AU - Butler, Sandra
AU - Atkinson, Jane C
AU - Adam, Stacey J
AU - Chang, Soju
AU - LaVange, Lisa
AU - Proschan, Michael
PY - 2023/7/10
Y1 - 2023/7/10
N2 - 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.
AB - 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.
U2 - 10.1001/jama.2023.11043
DO - 10.1001/jama.2023.11043
M3 - Article
C2 - 37428480
SN - 0098-7484
JO - JAMA
JF - JAMA
ER -