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.

Performance and Validation of Chronic Liver Disease Questionnaire-Hepatitis C Version (CLDQ-HCV) in Clinical Trials of Patients with Chronic Hepatitis C

“…Historically, HCV treatment with interferon-based regimens was associated with low SVR rates and substantial side effects [9,10]. Until recently, a triple therapy combination of pegylated interferon-alpha, ribavirin, and first-generation direct-acting antiviral (DAA) agents was the standard of care for treating CH-C [11]. Postapproval data for these regimens suggested relatively low efficacy and unfavorable safety profile.…”

HCV Kinetic Models and Their Implications in Drug Development

“…to evaluate the optimal dose of RBV in peg‐IFN/RBV‐treated patients . It can also encompass a more physiological model to dynamically adapt dosing regimens at the individual level, such as proposed by Laouenan et al ., who used individual predose concentrations of ribavirin and peg‐IFN to predict the evolution of hemoglobin and platelet levels, respectively, in patients treated with peg‐IFN/RBV and telaprevir or boceprevir …”

Prospective observational study on the pharmacokinetic properties of the Irrua ribavirin regimen used in routine clinical practice in patients with Lassa fever in Nigeria

“…For that purpose, a PK/tolerance model will be developed in order to relate the effect of the drugs on changes in longitudinal biological parameters as described previously for ribavirin in patients with HCV. 34…”