Randomised clinical trial: pre‐dosing with taribavirin before starting pegylated interferon vs. standard combination regimen in treatment‐naïve patients with chronic hepatitis C genotype 1

Abstract

SummaryBackgroundCombination therapy with the ribavirin (RBV) prodrug taribavirin (TBV) and pegylated interferon (PIFN) has produced lower rates of anaemia than with RBV and PIFN. Studies have demonstrated that the sharpest decline in viral load during TBV therapy occurs at Weeks 4 through 6, when TBV reaches steady-state blood levels.AimThe current proof-of-concept study was conducted to examine whether first-order viral kinetics could be influenced by pre-dosing TBV to steady state before introducing PIFN.MethodsTherapy-naïve patients with chronic hepatitis C virus (HCV) genotype 1 (G1) were randomised to receive (i) TBV 600 mg BID monotherapy for 4 weeks followed by combination therapy with PIFN [pre-dosing arm (n = 23)] or (ii) TBV administered concurrently with PIFN [standard dosing arm (n = 19)].ResultsMore patients achieved undetectable virus or a ≥2-log10 reduction of HCV RNA at Week 4 in the pre-dosing vs. the standard dosing arm [33% vs. 22% (P = 0.497)]. There was also a trend towards greater reduction in mean log10 change in HCV RNA in the pre-dosing vs. the standard dosing arm, which was statistically significant at Day 1 [−0.34 ± 0.46 vs. 0.09 ± 0.32 (P < 0.003)] but not at other time points up to Week 24. No significant difference was observed in the rates of anaemia (haemoglobin <10 g/dL) between study arms (4.5% vs. 5.3%).ConclusionsPre-dosing TBV prior to starting PIFN produces a trend towards improved efficacy although statistical significance was not reached in this small patient population. These results warrant larger clinical trials of TBV pre-dosing.

Effects of ribavirin monotherapy on the viral population in patients with chronic hepatitis C genotype 1: Direct sequencing and pyrosequencing of the HCV regions

“…These results could reflect a greater susceptibility of HCV to pegIFN following pre‐dosing with RBV, and thus enhanced effectiveness. In a recent study [Palmer et al, ], 42 chronic hepatitis C‐1 naïve patients were randomised to receive treatment either with four weeks of taribavirin in monotherapy, followed by combined treatment with pegIFN, or the combined treatment directly. Palmer et al [] also observed greater reductions in HCV‐RNA levels during the treatment, and suggested that pre‐dosing with taribavirin prior to starting pegIFN improves efficacy, although statistical significance was not achieved in this small number of patients.…”