Exploration of the optimal GS-441524 trough concentration for treating COVID-19

Abstract

Remdesivir (RDV) is the cornerstone for treating coronavirus disease 2019 (COVID-19). The active metabolite of RDV, GS-441524 (a nucleoside analog), has high inter-individual variability in plasma concentration; however, its concentration-response relationship is still unclear. This study investigated the target GS-441524 trough concentration for symptom improvement in COVID-19 pneumonia. This single-center, retrospective, observational study included COVID-19 pneumonia patients (≥15 years) who were administered RDV for ≥3 days from May 2020 to August 2021 at Saiseikai Futsukaichi Hospital. To determine the cut-off value of GS-441524 trough concentration on day 3, the achievement of the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS) ≤3 after RDV administration was evaluated using the cumulative incidence function (CIF) with the Gray test and time-dependent receiver operating characteristic (ROC) analysis. Multivariate logistic regression analysis was performed to determine the factors influencing GS-441524 target trough concentrations. Our analysis comprised 59 patients. The CIF revealed that GS-441524 trough concentration ≥70 ng/mL was associated with the achievement of NIAID-OS ≤3 (p = 0.047), which was significant based on the time-dependent ROC analysis. Factors influencing GS-441524 trough concentration ≥70 ng/mL included a decrease in eGFR (adjusted odds ratio [aOR] 0.96, 95% confidence interval [95% CI] 0.92-0.99, p = 0.027) and BMI ≥25 kg/m2 (aOR 0.26, 95% CI 0.07-0.86, p = 0.031). GS-441524 trough concentration ≥70 ng/mL is a predictor of efficacy in COVID-19 pneumonia. The presence of lower eGFR or BMI ≥25 kg/m2 was associated with achieving GS-441524 trough concentration ≥70 ng/mL.