Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial
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.
O'Halloran, J. A., Ko, E. R., Anstrom, K. J., Kedar, E., McCarthy, M. W., Panettieri, R. A., Maillo, M., Nunez, P. S., Lachiewicz, A. M., Gonzalez, C., Smith, P. B., de Tai, S. M., Khan, A., Lora, A. J., Salathe, M., Capo, G., Gonzalez, D. R., Patterson, T. F., Palma, C., Ariza, H., Lima, M. P., Blamoun, J., Nannini, E. C., Sprinz, E., Mykietiuk, A., Alicic, R., Rauseo, A. M., Wolfe, C. R., Witting, B., Wang, J. P., & Parra-Rodriguez, L. (2023). Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA, 330 (4), 328-339. https://doi.org/10.1001/jama.2023.11043