Optimal dosing frequency of pegylated interferon alfa-2b monotherapy for chronic hepatitis C virus infection

Background & Aims: Pegylated interferon alfa-2b (PEG-IFN-alfa 2b) has been shown to provide superior efficacy to IFN-alfa 2b in patients with chronic hepatitis C (predominantly genotype 1) infection as measured by viral clearance. This study was conducted to determine the optimal dosing regimen of PEG-IFN-alfa2b required to obtain a maximum decrease of hepatitis C viral RNA. Methods: This was a 24-week, open-label, multicenter, parallel-group, randomized, active-controlled trial in the United Kingdom, France, and Israel. Individuals (n = 61) with chronic hepatitis C infection, genotype 1, received IFN-alfa2b 3 mIU 3 times weekly for 24 weeks, or PEG-IFN-alfa2b 1.5 or 3.0 μg/kg/wk, as total weekly full or split doses, for 12 weeks. At week 12, serum RNA titer was measured, and all PEG-IFN-alfa2b patients continued with 1.5 μg/kg/wk for a further 12 weeks. Results: Mean serum hepatitis C RNA levels decreased in all groups at weeks 12 and 24. PEG-IFN-alfa2b 1.5 μg/kg/wk was superior to IFN-alfa2b in decreasing mean serum hepatitis C RNA (P <. 05 at week 12). The efficacy of split-dose PEG-IFN-alfa2b 1.5 or 3.0 μg/kg/wk regimens was not significantly different from full-dose PEG-IFN-alfa2b 1.5 μg/kg/wk. However, there was a significant decrease in neutrophil count in groups receiving PEG-IFN-alfa2b 3.0 μg/kg/wk or lower, multiple-dose per week regimens. Conclusions: PEG-IFN-alfa2b 1.5 μg/kg once weekly is the optimal dosing frequency for patients with chronic hepatitis C with predominantly genotype 1 infection. More frequent dosing or increasing the dose to 3.0 μg/kg/wk did not result in improved antiviral effects, but did decrease neutrophil counts. © 2005 by the American Gastroenterological Association.