Role of telaprevir plasma levels for predicting response to antiviral therapy in patients with hepatitis C virus genotype 1 infection

Abstract

Objective. Telaprevir (TVR)-based triple therapy has substantially improved cure rates of hepatitis C virus (HCV) genotype 1 infection but side effects are frequent and often severe. Therefore, response predictors are needed for early identification of patients not responding to TVR-based triple therapy. Material and methods. Forty-five patients (mean age: 54 ± 13 years; male gender: 60%; treatment-experienced: 82%; cirrhosis: 58%) with HCV genotype 1 infection were treated with a TVR-based triple-therapy regimen. TVR plasma levels were analyzed by liquid chromatography electrospray-ionization-tandem mass spectrometry at weeks 2, 4, 8, and 12 of antiviral therapy. On-treatment HCV RNA response was assessed at weeks 4, 12, and 24 by real-time polymerase chain reaction. Results. An extended rapid virological response (eRVR) and sustained virological response (SVR) was achieved in 21 of 45 patients (47%) and 36 of 45 (80%) patients, respectively. Mean ± standard deviation TVR plasma levels at week 2 were 3.4 ± 0.2 log₁₀ ng/ml and did not differ over time (when assessed at weeks 4, 8, and 12). TVR plasma levels at week 2 were significantly higher in patients who achieved an eRVR compared to those who did not achieve eRVR (3.5 ± 0.1 vs. 3.3 ± 0.2 log₁₀ ng/ml; p = 0.003) but were neither associated with SVR nor with treatment-related anemia. Conclusion. TVR plasma levels are associated with on-treatment response but not with overall treatment efficacy. Given the high overall response rates to TVR-based triple therapy, our data suggest that TVR trough levels may not be a useful predictor of treatment response, and routine drug-level monitoring is not required.

Key Words::

• drug monitoring, hepatitis C virus
• plasma levels
• telaprevir

Declaration of interest: Stefan Zeuzem has served as a speaker, a consultant, and/or advisory board member for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Merck&Co., Novartis, Roche/Genentech, Santaris Pharma A/S, and Vertex Pharmaceuticals. Christoph Sarrazin has served as a speaker, a consultant, and/or advisory board member for Abbott, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals, Merck/Merck Sharp&Dohme, Gilead Sciences, Novartis, and Siemens and Roche and has received research funding from Abbott, Qiagen, Roche, Siemens, Gilead Sciences, and Janssen Pharmaceuticals. Johannes Vermehren has served as a speaker for Bristol-Myers Squibb and Covidien. No financial support was received for this study.