Reducing Peg-IFN doses causes later virologic response or no response in HCV genotype 1 patients treated with Peg-IFN alfa-2b plus ribavirin.

Abstract

BACKGROUND:

The timing to the first undetectable hepatitis C virus (HCV) RNA level is strongly associated with sustained virologic response in pegylated interferon (Peg-IFN) plus ribavirin combination therapy for patients with chronic hepatitis C (CH-C) with genotype 1. This study was conducted to clarify the impact of drug exposure to Peg-IFN on the timing of HCV RNA negativity in Peg-IFN plus ribavirin combination therapy for CH-C patients with genotype 1.

METHODS:

A total of 1409 patients treated with Peg-IFN alfa-2b plus ribavirin were enrolled and classified into four categories according to the Peg-IFN dosage. Furthermore, 100 patients were extracted from each Peg-IFN dosage category to adjust for characteristic factors, using the propensity score method.

RESULTS:

Peg-IFN exposure was dose-dependently associated with the timing of HCV RNA negativity (p ≤ 0.001). The HCV RNA negative rate at week 4 decreased from 12% with a Peg-IFN dose of >1.5 μg/kg/week to 1-3% with a dose of <1.5 μg/kg/week (p ≤ 0.001), and at week 12 the rate had decreased from 44% with a dose of ≥1.2 μg/kg/week to 18% with a dose of <1.2 μg/kg/week (p = 0.001). Treatment failure (patients without a 1-log decrease of HCV RNA at week 4 or a 2-log decrease of HCV RNA at week 12, or positive at week 24) was found in 54-66% of patients given <1.2 μg/kg/week (p ≤ 0.001), and these patients accounted for 64% of the non-responders.

CONCLUSIONS:

The timing of HCV RNA negativity depends significantly on the Peg-IFN dose. Reducing the Peg-IFN dose can induce a later virologic response or non-response in HCV genotype 1 patients treated with Peg-IFN plus ribavirin.

• Authors: Tsugiko Oze, Naoki Hiramatsu, Changho Song, Takayuki Yakushijin, Sadaharu Iio, Yoshinobu Doi, Masahide Oshita, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Yoshiaki Inui, Taizo Hijioka, Shinji Tamura, Harumasa Yoshihara, Atsuo Inoue, Yasuharu Imai, Eijiro Hayashi, Michio Kato, Masanori Miyazaki, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Norio Hayashi, Tetsuo Takehara
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 47 Issue 3 Pg. 334-42 (Mar 2012) ISSN: 1435-5922 [Electronic] Japan
• PMID: 22109353 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• peginterferon alfa-2b

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Cohort Studies
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics, isolation & purification)
• Hepatitis C, Chronic (drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (administration & dosage, therapeutic use)
• Propensity Score
• Recombinant Proteins (administration & dosage, therapeutic use)
• Retrospective Studies
• Ribavirin (administration & dosage, therapeutic use)
• Time Factors
• Treatment Failure
• Treatment Outcome