Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results.

Abstract

UNLABELLED:

Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 microg/day and RBV, and 242 received CIFN 15 microg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 microg group and 10.7% (26/242) in the 15 microg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log(10) decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 mug group and 23% (7/31) in the 15 microg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 microg group and 13.1% (23/175) in the 15 microg group. In this same group of patients (F0-F3), if a >2-log(10) decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 microg and 15 microg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated.

CONCLUSION:

Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.

• Authors: Bruce R Bacon, Mitchell L Shiffman, Flavia Mendes, Reem Ghalib, Tarek Hassanein, Giuseppe Morelli, Shobha Joshi, Kenneth Rothstein, Paul Kwo, Norman Gitlin
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 49 Issue 6 Pg. 1838-46 (Jun 2009) ISSN: 1527-3350 [Electronic] United States
• PMID: 19291790 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon Type I
• Interferon alpha-2
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• Ribavirin
• interferon alfacon-1
• peginterferon alfa-2b
• peginterferon alfa-2a

Topics

• Antiviral Agents (administration & dosage)
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Hepatitis C, Chronic (drug therapy)
• Humans
• Interferon Type I (administration & dosage)
• Interferon alpha-2
• Interferon-alpha (therapeutic use)
• Male
• Middle Aged
• Polyethylene Glycols (therapeutic use)
• Recombinant Proteins
• Retreatment
• Ribavirin (administration & dosage)
• Treatment Failure