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

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.

Department

Description

Provenance

Citation

Published Version (Please cite this version)

10.1001/jama.2023.11043

Publication Info

O'Halloran, Jane A, Emily R Ko, Kevin J Anstrom, Eyal Kedar, Matthew W McCarthy, Reynold A Panettieri, Martin Maillo, Patricia Segura Nunez, et al. (2023). Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA, 330(4). pp. 328–339. 10.1001/jama.2023.11043 Retrieved from https://hdl.handle.net/10161/31115.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.

Scholars@Duke

Ko

Emily Ray Ko

Assistant Professor of Medicine

Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for infectious disease.

Smith

Phillip Brian Smith

Samuel L. Katz Distinguished Professor of Pediatrics

Dr. Smith completed his residency in pediatrics and a fellowship in neonatal medicine at Duke University Medical Center in 2004 and 2007, respectively. He completed an MHS in clinical research from Duke University in 2006 and an MPH in biostatistics from the University of North Carolina at Chapel Hill in 2009. His research is focused on pediatric drug safety, neonatal pharmacology, and the epidemiology of neonatal infections. Dr. Smith is or has been the protocol chair for more than 14 studies of drugs in infants and children. He is the Principal Investigator for the Environmental Influences on Child Health Outcomes (ECHO) Coordinating Center.

Wolfe

Cameron Robert Wolfe

Professor of Medicine

HIV infection, Transplant-related infectious diseases, general infectious diseases, Biological and Emergency Preparedness for hospital systems, influenza and respiratory viral pathogens

Der

Tatyana Der

Assistant Professor of Medicine
O'Brien

Sean Michael O'Brien

Associate Professor of Biostatistics & Bioinformatics

Statistical methods for healthcare provider profiling; observational studies; Bayesian data analysis.

Al-Khalidi

Hussein Rashid Al-Khalidi

Professor of Biostatistics & Bioinformatics

My research interest includes design and analysis of cardiovascular clinical trials, medical devices, survival analysis, group-sequential analysis, time-to-recurrent or multiple events, continuous-time Markov models, stochastic process, linear model, dose-response modeling, design of experiments and adaptive designs.

Halabi

Susan Halabi

James B. Duke Distinguished Professor

Design and analysis of clinical trials, statistical analysis of biomarker and high dimensional data, development and validation of prognostic and predictive models.


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