Original Investigation
July 10, 2023
Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial
Jane A. O’Halloran, Emily R. Ko, Kevin J. Anstrom, et al
JAMA. Published online July 10, 2023. doi:10.1001/jama.2023.11043
Question Do abatacept, cenicriviroc, or infliximab improve time to recovery for patients hospitalized with COVID-19 pneumonia compared with standard care?
Findings A randomized, double-masked, placebo-controlled master protocol clinical trial found that treatment with abatacept, cenicriviroc, or infliximab showed no statistically significant difference for the primary end point of time to recovery in patients with COVID-19 pneumonia vs standard care.
Meaning Abatacept, cenicriviroc, or infliximab did not decrease time to recovery for hospitalized patients with COVID-19 pneumonia.
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
