Summary and Introduction
Summary
Peginterferon-α plus ribavirin is the most effective therapy for chronic hepatitis C. This study was designed to evaluate the effect of peginterferon α-2a (40 kDa) plus ribavirin on sustained virological response (SVR) when administered for 24 vs 48 weeks in genotype 1 naïve patients. One hundred and seventeen patients were enrolled in this controlled trial. Genotype 1 patients were randomized to 24 weeks treatment vs 48 weeks treatment. Genotype non-1 patients received 24 weeks treatment as an observational group. Outcomes were SVR (defined by hepatitis C virus-RNA-negative at week 24 of follow-up) and tolerability across the study period. The end-of-treatment response was 59% for genotype 1 (24 weeks treatment), 80% for genotype 1 (48 weeks treatment) and 92% for genotype non-1 (24 weeks treatment). The end-of-follow-up response was 19% (95% confidence interval (CI): 7.2-36.4) (genotype 1, 24 weeks) and 48% (95% CI: 30.2-66.9; P = 0.0175) (genotype 1, 48 weeks). Among genotype non-1, SVR was 76% (95% CI: 62.3-86.5). There were no unexpected adverse events.Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon α-2a (40 kDa) and low-dose ribavirin and confirmed that they should be treated for 48 weeks. Safety profile was acceptable.
Introduction
It is estimated that 170 million people worldwide are chronically infected by hepatitis C virus (HCV)[1] and approximately 3-4 million become newly infected every year.[2] Focaccia et al.[3] have estimated the prevalence of HCV in the general population of the city of São Paulo (Brazil) as 1.4%, and the WHO[4] estimated an overall prevalence of 1.7% in the American continent.
At the present time, HCV genotype 1 is the most prevalent and accounts for approximately 60-80% of HCV infections overall. Patients with genotype 1 respond poorly to interferon-based treatment when compared with those with genotypes 2 and 3. Moreover, patients with high baseline HCV-RNA concentrations (> 800.000 IU/mL) and high-grade fibrosis (Metavir F3/4) have lower sustained virological responses (SVR).[5-7]
The 'pegylation' process of interferon α-2a involves an attachment of a 40 kDa PEG moiety producing peginterferon α-2a (40 kDa) (Pegasys®, Roche, São Paulo, Brazil). All pharmacological effects of interferon α-2a are preserved and its immunogenicity is reduced.[8,9] Given the improved pharmacokinetic characteristics of peginterferon α-2a (40 kDa),[8-10] a combination treatment period of only 24 weeks might be sufficient in patients infected with HCV genotype 1. The aim of this study was to investigate the effect of different treatment durations (24 weeks vs 48 weeks), with peginterferon α-2a (40 kDa) plus ribavirin (Copegus; Roche, São Paulo, Brazil) on the sustained response rate in chronic hepatitis C (CHC) patients with genotype 1 virus. The third treatment arm in this study enrolled only genotype non-1 patients in order to provide reference data.
