Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients receiving telaprevir-based triple therapy is useful for predicting virological response

摘要

Objectives: This prospective, pharmacokinetic study was done to investigate the impact of telaprevir plasma trough concentration (Ctrough) in the early stage of treatment on the response to telaprevir-based triple therapy for chronic hepatitis C patients. Methods: Participants were 70 chronic hepatitis C patients infected with genotype 1. All patients received 12 week triple therapy that included telaprevir (2250 mg/day), pegylated interferon-α2b (pegylated-IFNα2b) (60-150 μg/week) and ribavirin (600-1000 mg/day) followed by a 12 week dual therapy that included pegylated-IFNα2b and ribavirin. Plasma telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7 and 14. The study was registered as a clinical trial on the University Hospital Medical Information Network (ID 000009656). Results: The rates of undetectable hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24 weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%, respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999 μg/mL, respectively) were significantly higher than those of non-SVR patients (1.616, 1.788 and 2.314 μg/mL, respectively) (all P 0.05). Multiple logistic regression analysis of possible predictors of SVR extracted higher telaprevir Ctrough at day 3 (OR 1.012 by 0.001 μg/mL, P 0.0001) and interleukin 28B (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P 0.0001). Conclusions: Therapeutic drug monitoring of telaprevir in the early stage of treatment is useful in clinical practice for predicting the virological response of patients receiving telaprevir-based triple therapy.