Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial


Jane A. O'Halloran, Washington University St Louis, St Louis, Missouri.
Emily R. Ko, Duke University Health System, Durham, North Carolina.
Kevin J. Anstrom, University of North Carolina, Chapel Hill.
Eyal Kedar, Rochester Regional HealthFollow
Matthew W. McCarthy, Weill Cornell Medicine, New York, New York.
Reynold A. Panettieri, Robert Wood Johnson Medical School, New Brunswick, New Jersey.
Martin Maillo, Sanatorio Diagnostico, Santa Fe, Argentina.
Patricia Segura Nunez, Hospital Nacional Hipolito Unanue, Lima, Peru.
Anne M. Lachiewicz, University of North Carolina, Chapel Hill.
Cynthia Gonzalez, National Center for Advancing Translational Sciences, Bethesda, Maryland.
P Brian Smith, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Sabina Mendivil-Tuchia de Tai, Hospital Central de la Fuerza Aerea del Peru, Lima, Peru.
Akram Khan, Oregon Health and Science University, Portland.
Alfredo J. Lora, University of Illinois at Chicago.
Matthias Salathe, University of Kansas Medical Center, Kansas City.
Gerardo Capo, Trinitas Hospital, Elizabeth, New Jersey.
Daniel Rodríguez Gonzalez, Nuevo Hospital Civil de Guadalajara Juan I. Menchaca, Guadalajara, Mexico.
Thomas F. Patterson, University of Texas Health Science Center at San Antonio.
Christopher Palma, University of Rochester School of Medicine and Dentistry, Rochester, New York.
Horacio Ariza, Clinica Central SA, Villa Regina, Argentina.
Maria Patelli Lima, Hospital e Maternidade Celso Pierro-PUC Campinas, Campinas, Brazil.
John Blamoun, MidMichigan Medical Center, Midland.
Esteban C. Nannini, Sanatorio Britanico, Santa Fe, Argentina.
Eduardo Sprinz, Hospital de Clinicas de Porto Alegre HCPA, Porto Alegre, Brazil.
Analia Mykietiuk, Instituto Medico Platense, La Plata, Argentina.
Radica Alicic, Providence Medical Research Center, Spokane, Washington.
Adriana M. Rauseo, Washington University St Louis, St Louis, Missouri.
Cameron R. Wolfe, Duke University Health System, Durham, North Carolina.
Britta Witting, Weill Cornell Medicine, New York, New York.
Jennifer P. Wang, University of Massachusetts Medical Center, Worcester.
Luis Parra-Rodriguez, Washington University St Louis, St Louis, Missouri.



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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.

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