BACKGROUND/AIMS: To compare the pharmacokinetics, pharmacodynamics, and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1. METHODS:Thirty-six patients were randomised to peginterferon alfa-2b (1.5 microg/kg/week) or peginterferon alfa-2a (180 microg/week) for 4 weeks, then in combination with ribavirin (13 mg/kg/day) for a further 4 weeks. The pharmacokinetic profile of both peginterferons, mRNA expression of a selected group of interferon-induced gene transcripts, and serum HCV-RNA levels were assessed. RESULTS: Patients receiving peginterferon alfa-2b had significantly greater up-regulation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a. Correspondingly, patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA. A greater proportion of peginterferon alfa-2b patients achieved a > or = 2.0 log10 reduction in serum HCV-RNA levels by week 8 (72% vs 44% of peginterferon alfa-2a patients, P = 0.09). There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a. CONCLUSIONS: These findings suggest that the biological activity, measured by early interferon-induced gene transcripts and early antiviral responsiveness, may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.
RCT Entities:
BACKGROUND/AIMS: To compare the pharmacokinetics, pharmacodynamics, and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1. METHODS: Thirty-six patients were randomised to peginterferon alfa-2b (1.5 microg/kg/week) or peginterferon alfa-2a (180 microg/week) for 4 weeks, then in combination with ribavirin (13 mg/kg/day) for a further 4 weeks. The pharmacokinetic profile of both peginterferons, mRNA expression of a selected group of interferon-induced gene transcripts, and serum HCV-RNA levels were assessed. RESULTS:Patients receiving peginterferon alfa-2b had significantly greater up-regulation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a. Correspondingly, patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA. A greater proportion of peginterferon alfa-2b patients achieved a > or = 2.0 log10 reduction in serum HCV-RNA levels by week 8 (72% vs 44% of peginterferon alfa-2apatients, P = 0.09). There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a. CONCLUSIONS: These findings suggest that the biological activity, measured by early interferon-induced gene transcripts and early antiviral responsiveness, may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.
Authors: C Xu; S Gupta; G Krishna; D Cutler; S Wirth; C Galoppo; M Ciocca; K Kolz; S Noviello; V Sniukiene Journal: Eur J Clin Pharmacol Date: 2013-08-24 Impact factor: 2.953
Authors: Michael T Dill; Zuzanna Makowska; Gaia Trincucci; Andreas J Gruber; Julia E Vogt; Magdalena Filipowicz; Diego Calabrese; Ilona Krol; Daryl T Lau; Luigi Terracciano; Erik van Nimwegen; Volker Roth; Markus H Heim Journal: J Clin Invest Date: 2014-02-24 Impact factor: 14.808