Infliximab Pharmacokinetics, Dosing, and Response in Hospitalized Patients with COVID-19 Pneumonia: A Secondary Analysis of a Multinational Randomized Clinical Trial (ACTIV-1 IM).

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 (AUC0-28). Logistic regression modeling was used to relate AUC0-28 to the primary outcome of 28-day mortality, adjusted for age. The relationship between AUC0-28 and the secondary outcome of time to recovery was evaluated using a Fine-Gray model, adjusted for age, with death as a competing risk. AUC0-28 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 AUC0-28 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 AUC0-28 was associated with a greater probability of recovery; an AUC0-28 ≤ 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 AUC0-28 >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 AUC0-28 of at least 17,400 mg h/L, particularly those <100 kg and those with the highest baseline disease severity.

Duke Scholars

Author Stephen Joseph Balevic Pediatrics, Rheumatology

Author Christoph Paul Vincent Hornik Pediatrics, Critical Care Medicine

Author Daniel Kelly Benjamin Jr. Pediatrics, Infectious Diseases

Author Christopher Lindsell Biostatistics & Bioinformatics, Division of Biostatistics

Author Phillip Brian Smith Pediatrics, Neonatology

Author Daniel Gonzalez Medicine, Clinical Pharmacology