Daily interferon induction regimen using different manufactured interferons (alpha-2a or alpha-2b) in combination with ribavirin for treatment of chronic hepatitis C: a prospective randomized study

Abstract

Background - Studies on hepatitis C virus kinetics showed that serum levels of interferon fall 48 h after drug administration, when viral load is increasing again. Previously to the availability of pegylated interferon, daily induction therapy with standard interferon was under evaluation. Aims - To evaluate the safety and effi cacy of interferon alpha daily induction regimen in combination with ribavirin. Patients and methods - A randomized trial including 93 patients with chronic hepatitis C was carried out. On satisfying all eligibility criteria, patients were randomly allocated to two different treatment groups: 44 individuals in treatment arm A: IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily for 48 weeks (IFN TIW) and 49 individuals in treatment arm B: IFN 3 MU daily + ribavirin 1.0-1.2 g daily for 12 weeks followed by IFN 3 MU thrice weekly + ribavirin 1.0-1.2 g daily, until completion of 48 weeks of therapy (IFN QD). HCV genotyping was obtained in 85 subjects. A negative HCV-RNA 6 months after cessation of therapy was considered a sustained virological response. Results - Eighty three patients completed treatment, fi ve dropped out (one from IFN TIW and four from IFN QD) and in fi ve patients therapy was discontinued due to medical request (two from IFN TIW and three from IFN QD). There was no statistically signifi cant difference between groups with respect to therapy interruption. The frequency of cirrhosis was 29%, similar in both groups. In the “intention to treat” analysis the overall sustained virological response was 39.8%. There was no signifi cant difference in sustained virological response rate between both treatment strategies (36.4% IFN TIW vs 42.9% IFN QD). In the 83 patients who fi nished the trial, sustained virological response was 44.6%. Among subjects with HCV genotype-1, the sustained virological response was 42% (40.9% IFN TIW vs 42.9% IFN QD) and among patients with HCV genotype 2 or 3, the sustained virological response was 55.6% (50% IFN TIW vs 63.6% IFN QD). Conclusions – Combination therapy had an overall sustained virological response rate of 39.8% (“intention to treat analysis”). There was no difference with respect to sustained virological response rates between patients who used daily induction schedule compared to standard regimen. Adverse events, even more frequent in the daily induction group, did not interfere with the treatment strategies.