Pegylated Interferon Monotherapy for Chronic Hepatitis C

Interferon (IFN) α-2a has been attached to a branched 40-kD PEG molecule and IFN α-2b to a linear 12-kD PEG molecule leading to elimination half-lives of approximately 75 and approximately 30 hours, respectively. In one pivotal trial, 531 patients with chronic hepatitis C were assigned to receive either 180 μg of pegylated IFN α-2a once weekly for 48 weeks or 3 × 6 mIU standard IFN for 12 weeks, followed by 3 × 3 mIU for 36 weeks. Sustained virological response rates were 39 and 19% for pegylated and standard IFN α-2a, respectively. In a second trial in patients with hepatitis C virus (HCV)-associated cirrhosis and bridging fibrosis, sustained virological response rates were 8% (3 × 3 mIU IFN three times a week), 15% (90 μg PEG-IFN α-2a four times a week), and 30% (180 μg PEG-IFNα-2a four times a week). In a third trial, 1219 patients with chronic hepatitis C were randomly assigned to receive either standard IFN α-2b (3 × 3 mIU) or once weekly pegylated IFN α-2b (0.5, 1.0, or 1.5 μg/kg). Sustained virological response rates were highest in the 1.0 μg/kg dose and achieved 25% compared with 12% in the standard IFN group. In conclusion, each regimen of pegylated IFN given once weekly is more effective than a regimen of standard IFN given three times weekly.

Hepatitis C virus - pegylated interferon alfa-2a (40 kD) - pegylated interferon alfa-2b - standard interferon - monotherapy - histology - viral kinetics - virological response

REFERENCES

• 1 Barouki F M, Witter F R, Griffin D E et al.. Time course of interferon levels, antiviral state, 2′,5′-oligoadenylate synthetase and side effects in healthy men.  J Interferon Res. 1987;  7 29-39
• 2 Wills R J. Clinical pharmacokinetics of interferons.  Clin Pharmacokinet. 1990;  19 390-399
• 3 Nucci M L, Shorr R, Abuchowski A. The therapeutic value of poly(ethylene glycol)-modified proteins.  Adv Drug Deliv Rev. 1991;  6 133-151
• 4 Reddy K R. Development and pharmacokinetics and pharmacodynamics of pegylated interferon alfa-2a (40 kD).  Semin Liver Dis. 2004;  24(suppl 2) 33-38
• 5 Glue P, Rouzier-Panis R, Raffanel C et al.. A dose-ranging study of pegylated interfern alfa-2b and ribavirin in chronic hepatitis C.  Hepatology. 2000;  32 647-653
• 6 Reddy K R, Wright T L, Pockros P J et al.. Efficacy and safety of pegylated (40-kd) interferon α-2a compared with interferon α-2a in non-cirrhotic patients with chronic hepatitis C.  Hepatology. 2001;  33 433-438
• 7 Zeuzem S, Feinman S V, Rasenack J et al.. Peginterferon alfa-2a in patients with chronic hepatitis C.  N Engl J Med. 2000;  343 1666-1672
• 8 Heathcote E J, Shiffman M L, Cooksley W GE et al.. Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.  N Engl J Med. 2000;  343 1673-1680
• 9 Zeuzem S, Herrmann E, Lee J-H et al.. Viral kinetics in patients with chronic hepatitis C treated with standard of peginterferon α2a.  Gastroenterology. 2001;  120 1438-1447
• 10 Neumann A U, Lam N P, Dahari H et al.. Hepatitis C viral dynamics in vivo and the anti-viral efficacy of interferon α therapy.  Science. 1998;  282 103-107
• 11 Zeuzem S, Schmidt J M, Lee J-H, Rüster B, Roth W K. Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo.  Hepatology. 1996;  23 366-371
• 12 Ascione A, De Luca M, Canestrini C et al.. Efficacy of high dose of recombinant alfa 2b interferon on long term response in chronic hepatitis C and cirrhosis: perspective randomized multicentre study.  Ital J Gastroenterol Hepatol. 1998;  30 517-523
• 13 Schalm S W, Weiland O, Hansen B E et al.. Interferon ribavirin for chronic hepatitis C with and without cirrhosis: analysis of individual patient data of six controlled trials.  Gastroenterology. 1999;  117 408-413
• 14 Valla D C, Chevallier M, Marcelin P et al.. Treatment of hepatitis C virus related cirrhosis: a randomized, controlled trial of interferon alfa-b versus no treatment.  Hepatology. 1999;  29 1870-1875
• 15 Shiratori Y, Yokosuka O, Nakata R et al.. Prospective study of interferon therapy for compensated cirrhotic patients with chronic hepatitis C by monitoring serum hepatitis C RNA.  Hepatology. 1999;  29 1573-1580
• 16 Lindsay K, Trepo C, Heintges T et al.. A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.  Hepatology. 2001;  34 395-403
• 17 Buti M, Sanchez-Avila F, Lurie Y et al.. Viral kinetics in genotype 1 chronic hepatitis C patients during therapy with 2 different doses of peginterferon alfa-2b plus ribavirin.  Hepatology. 2002;  35 930-936
• 18 Poynard T, Marcellin P, Lee S S et al.. Randomized trial of interferon α 2b plus ribavirin for 48 weeks or for 24 weeks versus interferon α2b plus placebo for 48 weeks for treatment of chronic hepatitis C virus.  Lancet. 1998;  352 1426-1432