Potential conflict of interest: Nothing to report.
Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results†
Article first published online: 2 FEB 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 49, Issue 6, pages 1838–1846, June 2009
How to Cite
Bacon, B. R., Shiffman, M. L., Mendes, F., Ghalib, R., Hassanein, T., Morelli, G., Joshi, S., Rothstein, K., Kwo, P. and Gitlin, N. (2009), Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology, 49: 1838–1846. doi: 10.1002/hep.22871
- Issue published online: 28 MAY 2009
- Article first published online: 2 FEB 2009
- Accepted manuscript online: 2 FEB 2009 12:00AM EST
- Manuscript Accepted: 24 JAN 2009
- Manuscript Received: 21 AUG 2008
- InterMune, Inc.
- Valeant Pharmaceuticals International
- Three Rivers Pharmaceuticals
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 μg/day and RBV, and 242 received CIFN 15 μg/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 μg group and 10.7% (26/242) in the 15 μg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log10 decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 μg group and 23% (7/31) in the 15 μg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 μg group and 13.1% (23/175) in the 15 μg group. In this same group of patients (F0-F3), if a >2-log10 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 μg and 15 μg 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. (HEPATOLOGY 2009.)