Publication date: Jul 10, 2023
Immune dysregulation contributes to poorer outcomes in COVID-19. To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. 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. 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). 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. 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. Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. ClinicalTrials. gov Identifier: NCT04593940.
Open Access PDF