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

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 (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 17,400 mg h/L, albeit at a lower rate (1.18-fold higher [95% CI 1.07-1.32]), P <100 kg and those with the highest baseline disease severity.