Pegylated Interferon α-2b, Ribavirin and Amantadine for Chronic Hepatitis C
- 67 Downloads
In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon α-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon α-2b at a dose of 1.5 μg/kg weekly with ribavirin, 1000–1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon α-2b, 0.5 μg/kg weekly, ribavirin, 1000–1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (< 50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27 ± 5.76 years; their body mass index (BMI) was 28.87 ± 5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242 ± 698,030 IU/mL, with a baseline ALT of 107.25 ± 79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, < 8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0–2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon α-2b and ribavirin does not seem to increase the efficacy of this antiviral regimen.
Key Wordschronic hepatitis C amantidine pegylated interferon α-2b ribavirin antiviral therapy HCV therapy Triple combination Amantadine
Unable to display preview. Download preview PDF.
- 1.Hoofnagle JH: Course and outcome of hepatitis C. Hepatology 36:21S–29S, 2002Google Scholar
- 3.National Institutes of Health: Consensus development conference statement; Management of hepatitis C. Hepatology 36 (5) (Suppl 1): S3–S20, 2003Google Scholar
- 8.Davis GL, Esteban-Mur R, Rustgi V, et al.: Interferon alfa-2b alone or in combination with ribavirin or the treatment of relapse of chronic hepatitis C. N Engl J Med 339:1493–1499, 2001Google Scholar
- 11.Shiffman ML, Hofmann CM, Gabbay J, et al.: Treatment of chronic hepatitis C in patients who failed interferon monotherapy: effects of higher doses of interferon and ribavirin combination therapy. The Virginia cooperative hepatitis treatment group. Am J Gastroenterol 95(10):2928–2935, 2000PubMedGoogle Scholar
- 13.Schiffman M: HALT-C Trial Investigators. Retreatment of HCV non-responders with peginterferon and ribavirin: results from the lead-in phase of the Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) trial. Hepatology 36(4, Pt 2):295A (abstract 527), 2002Google Scholar
- 15.Younossi Z, Perillo R: The roles of amantadine, rimantadine, ursodeoxycholic acid and NSAID’s alone or in combination with alpha interferon in the treatment of chronic hepatitis C. Sem in Liver Disease 19:95–102, 1999Google Scholar
- 19.Manns MP, McHutchison JG, Gordon SC, et al.: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for intial treatment of chronic hepatitis C: a randomized trial. Lancet 22;358(9286):958–965, 2001Google Scholar
- 23.Martin L, Sheridan M, Younossi Z: Health-related Quality of Life Instruments and Chronic Liver Disease. Clin Perspect Gastroenterol 5(1):60–63, 2002Google Scholar