A Model-Based Illustrative Exploratory Approach to Optimize the Dosing of Peg-IFN/RBV in Cirrhotic Hepatitis C Patients Treated With Triple Therapy

Abstract

Hézode et al. recently reported the frequent occurrence of anemia and thrombocytopenia in the ANRS-CO20-CUPIC cohort of hepatitis C virus (HCV) cirrhotic experienced patients treated with pegylated-interferon (Peg-IFN), ribavirin (RBV), and telaprevir or boceprevir.1,2 Using frequent measurements of serum drug concentrations, hemoglobin, and platelet concentrations obtained in 15 patients of this cohort, we show how an on-treatment model-based approach could be used to individualize dose regimen and avoid the occurrence of RBV-induced anemia and Peg-IFN-induced thrombocytopenia.

Figure 1

Relationship between: (a) RBV predicted trough serum concentration at steady state (C_ss) and predicted blocking production of hemoglobin () and (b) Peg-IFN predicted trough concentration at steady state (C_ss) and predicted blocking production of platelets (). Nine patients in the telaprevir group in a (black) and six patients in the boceprevir group (gray). Eleven patients in the Peg-IFN-α2a group in b (black) and three patients in the Peg-IFN-α2b group (gray). The lines denote the predictions with the mean blocking production and the dotted lines denote 95% confidence interval computed with the standard errors predicted by the Fisher Information Matrix.