Peginterferon α-2a and ribavirin versus peginterferon α-2a monotherapy in early virological responders and peginterferon α-2a and ribavirin versus peginterferon α-2a, ribavirin and amantadine triple therapy in early virological nonresponders:: the SMIEC II trial in naive patients with chronic hepatitis C

Objective The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (< 50 IU/ ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week. Methods A total of 210 interferon-naive patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n = 57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups. Results Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 672% in the PEG-IFN + RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN + RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041). Conclusion In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.