Telaprevir-Based Triple Therapy for Chronic Hepatitis C
Telaprevir-Based Triple Therapy for Chronic Hepatitis C
Background Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications.
Aim To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting.
Methods This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3–4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV).
Results The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection.
Conclusions The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.
The estimated global prevalence of hepatitis C virus (HCV) infection in 2004 was 2.2%, and 30–40% of patients with chronic hepatitis C will eventually develop cirrhosis, unless HCV is eradicated with anti-viral treatment. The goal of therapy for chronic hepatitis C is to eradicate HCV infection, as indicated by sustained virological response (SVR), which has been associated with reduced development of hepatocellular carcinoma, hepatic decompensation, and prolonged survival. Therefore, anti-viral treatment should be initiated promptly for patients with advanced fibrosis (METAVIR score F3–4). However, advanced fibrosis lowers the chance of treatment success by non pegylated interferon, pegylated interferon-alpha (PEG-IFNα), and the combination of PEG-IFNα and ribavirin (RBV) for HCV genotype 1 patients.
Since 2011, the standard of care regimen for the treatment of HCV genotype 1 has been a combination of a non structural (NS) 3/4A protease inhibitor, PEG-IFNα, and RBV. The 2 first-generation NS3/4A protease inhibitors, telaprevir (TVR) and boceprevir, have been approved worldwide. In phase III trials, SVR rates have dramatically increased, especially for patients with prior relapse or no or mild fibrosis (METAVIR score F0–2).
Recently, the CUPIC study from France carried out in a clinical practice setting, showed a safety profile for TVR- and boceprevir-based triple therapy for cirrhotic patients. Our recent study suggested that inosine triphosphatase (ITPA) polymorphism (rs1127354) is useful for predicting the development of severe anaemia during TVR-based triple therapy. Even though we practice in a rapidly changing environment because of the introduction of next generation of direct acting anti-virals (DAAs) and the potential use of IFN-free regimens in the near future, little detailed data related to the virological efficacy of treatment with DAAs for advanced fibrosis patients have been reported in clinical practice.
The aims of this prospective, multicentre study were to evaluate the efficacy and safety of TVR-based triple therapy for chronic hepatitis C genotype 1 patients with advanced fibrosis. We attempted to determine if interleukin 28B (IL28B) single nucleoside polymorphisms (SNPs), adverse effects, and treatment adherence were related to the treatment outcome of patients with advanced fibrosis.
Abstract and Introduction
Abstract
Background Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications.
Aim To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting.
Methods This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3–4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV).
Results The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection.
Conclusions The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.
Introduction
The estimated global prevalence of hepatitis C virus (HCV) infection in 2004 was 2.2%, and 30–40% of patients with chronic hepatitis C will eventually develop cirrhosis, unless HCV is eradicated with anti-viral treatment. The goal of therapy for chronic hepatitis C is to eradicate HCV infection, as indicated by sustained virological response (SVR), which has been associated with reduced development of hepatocellular carcinoma, hepatic decompensation, and prolonged survival. Therefore, anti-viral treatment should be initiated promptly for patients with advanced fibrosis (METAVIR score F3–4). However, advanced fibrosis lowers the chance of treatment success by non pegylated interferon, pegylated interferon-alpha (PEG-IFNα), and the combination of PEG-IFNα and ribavirin (RBV) for HCV genotype 1 patients.
Since 2011, the standard of care regimen for the treatment of HCV genotype 1 has been a combination of a non structural (NS) 3/4A protease inhibitor, PEG-IFNα, and RBV. The 2 first-generation NS3/4A protease inhibitors, telaprevir (TVR) and boceprevir, have been approved worldwide. In phase III trials, SVR rates have dramatically increased, especially for patients with prior relapse or no or mild fibrosis (METAVIR score F0–2).
Recently, the CUPIC study from France carried out in a clinical practice setting, showed a safety profile for TVR- and boceprevir-based triple therapy for cirrhotic patients. Our recent study suggested that inosine triphosphatase (ITPA) polymorphism (rs1127354) is useful for predicting the development of severe anaemia during TVR-based triple therapy. Even though we practice in a rapidly changing environment because of the introduction of next generation of direct acting anti-virals (DAAs) and the potential use of IFN-free regimens in the near future, little detailed data related to the virological efficacy of treatment with DAAs for advanced fibrosis patients have been reported in clinical practice.
The aims of this prospective, multicentre study were to evaluate the efficacy and safety of TVR-based triple therapy for chronic hepatitis C genotype 1 patients with advanced fibrosis. We attempted to determine if interleukin 28B (IL28B) single nucleoside polymorphisms (SNPs), adverse effects, and treatment adherence were related to the treatment outcome of patients with advanced fibrosis.