Impact of High-Dose Peginterferon Alfa-2A on Virological Response Rates in Patients with Hepatitis C Genotype 1: a Randomized Controlled Trial

This study tested the hypothesis that high-dose peginterferon alfa-2a (PEG-IFN alpha-2a) for the first 12 weeks would increase early and sustained virological response (SVR) rates in patients with chronic hepatitis C genotype 1. Eight hundred ninety-six patients were randomized 1:1 to 360 mu g (n = 448) or 180 mu g (n = 448) PEG-IFN alpha-2a weekly plus ribavirin at 1000-1200 mg/day for 12 weeks, followed by 36 weeks of 180 mu g PEG-IFN alpha-2a weekly plus ribavirin at 1000-1200 mg/day with 871 patients evaluable for the intention-to-treat analysis. Virological responses were assessed by TaqMan (limit of detection 15 IU/mL) at week 4, 8, 12, 24, 48 (end of therapy), and 24 weeks following therapy (SVR). Undetectable hepatitis C virus RNA rates were significantly higher among patients receiving high-dose induction therapy at week 4 (36% versus 26%, P < 0.005), week 8 (61% versus 50%, P < 0.005), and week 12 (74% versus 62%, P < 0.005). However, SVR was not significantly different between patients receiving high-dose (53%) and standard (50%) therapy. Significant baseline prognostic factors for SVR included age, sex, race, histological stage, and viral load. SVR was considerably higher among patients with no or minimal fibrosis (64% and 60%, respectively) compared to those with severe fibrosis/cirrhosis (28% and 24%, respectively). The frequency of serious adverse events and drug discontinuations were similar in both groups, whereas PEG-IFN dose modification, weight and appetite reduction, and grade IV neutropenia were significantly higher in the induction arm. Conclusion: Induction dosing with 360 mu g/week PEG-IFN alpha-2a for 12 weeks was well tolerated and enhanced early virological response but not SVR rates. The high SVR rates in patients with minimal fibrosis highlight the benefit of early treatment in patients with hepatitis C virus genotype 1. (HEPATOLOGY 2009;50:1045-1055.)