• Open Access

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

Authors

  • M. Palmer,

    Corresponding author
    • Liver Center of Long Island, Plainview, NY, USA
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  • R. Rubin,

    1. Digestive Healthcare of Atlanta, Atlanta, GA, USA
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  • V. Rustgi,

    1. Metropolitan Research, Georgetown Medical Center, Fairfax, VA, USA
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  • Taribavirin Viral Kinetic Study Group

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    • Terry Box, MD, Mountain West Gastroenterology Research Office; Richard Chasen, MD, Maryland Digestive Disease Research; Eliot Godofsky, MD, Bach and Godofsky; Joanne Imperial, MD, San Mateo Medical Center; Lennox Jeffers, MD, University of Miami; Karen Lindsay, MD, University of Southern California; Victor Navarro, MD, Jefferson University; Melissa Palmer, MD, Liver Center of Long Island; Raymond Rubin, MD, Digestive Healthcare of Georgia; Vinod Rustgi, MD, Georgetown Medical Center; John Santoro, DO, Atlantic Gastroenterology Associates.

  • Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms

Correspondence to:

Dr M. Palmer, 1097 Old Country Road, Plainview, NY 11803, USA.

E-mail: drpalmer@liverdisease.com

Summary

Background

Combination 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.

Aim

The 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.

Methods

Therapy-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)].

Results

More 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% (= 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 (< 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%).

Conclusions

Pre-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.

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