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

Abstract

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-alfa 2b 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-alfa 2b 3 mIU 3 times weekly for 24 weeks, or PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk, as total weekly full or split doses, for 12 weeks. At week 12, serum RNA titer was measured, and all PEG-IFN-alfa 2b patients continued with 1.5 microg/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-alfa 2b 1.5 microg/kg/wk was superior to IFN-alfa 2b in decreasing mean serum hepatitis C RNA ( P < .05 at week 12). The efficacy of split-dose PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk regimens was not significantly different from full-dose PEG-IFN-alfa 2b 1.5 microg/kg/wk. However, there was a significant decrease in neutrophil count in groups receiving PEG-IFN-alfa 2b 3.0 microg/kg/wk or lower, multiple-dose per week regimens.

CONCLUSIONS:

PEG-IFN-alfa 2b 1.5 microg/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 microg/kg/wk did not result in improved antiviral effects, but did decrease neutrophil counts.

• Authors: Yoav Lurie, Regine Rouzier-Panis, George J M Webster, Geoffrey M Dusheiko, Mark Laughlin, Mary L Jackson, Ran Oren
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 3 Issue 6 Pg. 610-5 (Jun 2005) ISSN: 1542-3565 [Print] United States
• PMID: 15952104 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon alpha-2
• Interferon-alpha
• RNA, Viral
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2b

Topics

• Adolescent
• Adult
• Aged
• Antiviral Agents (administration & dosage, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• France
• Genotype
• Hepacivirus (genetics, pathogenicity)
• Hepatitis C, Chronic (blood, drug therapy, virology)
• Humans
• Interferon alpha-2
• Interferon-alpha (administration & dosage, therapeutic use)
• Israel
• Male
• Middle Aged
• Polyethylene Glycols
• RNA, Viral (blood, genetics)
• Recombinant Proteins
• Reverse Transcriptase Polymerase Chain Reaction
• Safety
• Treatment Outcome
• United Kingdom
• Virulence (drug effects, genetics)