Infliximab Pharmacokinetics, Dosing, and Response in Hospitalized Patients with COVID‐19 Pneumonia: A Secondary Analysis of a Multinational Randomized Clinical Trial (ACTIV‐1 IM)
Year: 2025
Type: article
Abstract: Infliximab may play an important role in reducing mortality in severe COVID‐19, though optimal dosing is unknown. This secondary analysis of the ACTIV‐1 IM trial characterized infliximab pharmacokinetics and outcomes in patients hospitalized with severe COVID‐19. ACTIV‐1 IM included patients admitted with COVID‐19 pneumonia who received infliximab in addition to routine care. Infliximab was administered as a single 5‐mg/kg intravenous dose. The primary exposure variable was predicted infliximab concentrations over 28 days (AUC 0‐28 ). Logistic regression modeling was used to relate AUC 0‐28 to the primary outcome of 28‐day mortality, adjusted for age. The relationship between AUC 0‐28 and the secondary outcome of time to recovery was evaluated using a Fine–Gray model, adjusted for age, with death as a competing risk. AUC 0‐28 was higher in patients who did not die versus those who died, with a median (range) of 20,681 mg h/L (8379‐60,322) versus 17,392 (9543‐43,145), P < .001. A 5000‐unit increase in AUC 0‐28 was associated with decreased mortality (OR 0.62, 95% CI 0.43‐0.88, P = .008) and decreased composite safety events (OR 0.57, 95% CI 0.45‐0.71, P < .001). Higher AUC 0‐28 was associated with a greater probability of recovery; an AUC 0‐28 ≤ 17,400 mg h/L was associated with a 3.45‐fold higher (95% CI 2.23‐5.34) probability of recovery at Day 28, as was an AUC 0‐28 >17,400 mg h/L, albeit at a lower rate (1.18‐fold higher [95% CI 1.07‐1.32]), P < .002 for both. Overall, 113/390 (29.0%) patients did not achieve an optimal predicted infliximab AUC 0‐28 of at least 17,400 mg h/L, particularly those <100 kg and those with the highest baseline disease severity.
DOI: 10.1002/jcph.70057
Authors: Stephen J. Balevic, Daniel Gonzalez, P. Brian Smith, William G. Powderly, Andreas Schmid, Ashley Kang, Matthew W. McCarthy, Linda K. Shaw, Christopher J. Lindsell, Sam Bozzette, Richard M. W. Hoetelmans, Christoph P. Hornik, Daniel K. Benjamin Jr, for the ACTIV‐1 IM Study Group Members
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences, Duke Clinical Research Institute, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1705870301, G1859754121, Duke CTSA, G2490806176, G2762714575, G2824222223, Center for Clinical and Translational Science, G3117983185, G343705321, G3797236039, Tufts Clinical and Translational Science Institute, G435399002, G436035484, G4622355042, G477853788, G5139652136, G5275218458, Physiologically-Based Pharmacokinetic Modeling to Guide Drug Dosing in Children with Obesity, Expanding Translational Research in Arkansas, North Carolina Translational and Clinical Science Institute (NC TraCS), G691201058, Frontiers Clinical and Translational Science Institute at the University of Kansas, Mayo Clinic Center for Clinical and Translational Science (CCaTS), Kentucky Center for Clinical and Translational Science, UCLA Clinical and Translational Science Institute
OpenAlex ID: W4411151906