Improved outcomes in patients with hepatitis C with difficult-to-treat characteristics: randomized study of higher doses of peginterferon alpha-2a and ribavirin.

Abstract

UNLABELLED:

Treatment response remains suboptimal for many patients with chronic hepatitis C, particularly those with genotype 1 and high levels of viremia. The efficacy of high-dose regimens of peginterferon alfa-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses. Eligible treatment-naïve adults with genotype 1 infection, hepatitis C virus (HCV) RNA >800,000 IU/mL and body weight >85 kg were randomized to double-blind treatment with peginterferon alfa-2a at 180 or 270 microg/week plus ribavirin at 1200 or 1600 mg/day for 48 weeks (four regimens were evaluated). The primary endpoint was viral kinetics during the first 24 weeks of therapy. Among patients receiving peginterferon alfa-2a (270 microg/week) the magnitude of HCV RNA reduction was significantly greater than for patients randomized to the conventional dose of peginterferon alfa-2a (180 microg/week) for the pairwise comparison for ribavirin at 1600 mg/day (P = 0.036) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day (P = 0.060). Patients randomized to the highest doses of peginterferon alfa-2a (270 microg/week) and ribavirin (1600 mg/day) experienced the numerically highest rates of sustained virologic response (HCV RNA < 50 IU/mL) and the lowest relapse rate (47% and 19%, respectively). The arm with the higher doses of both drugs was less well-tolerated than the other regimens.

CONCLUSION:

Higher fixed doses of peginterferon alfa-2a (270 microg/week) and ribavirin (1600 mg/day) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult-to-treat characteristics.

• Authors: Michael W Fried, Donald M Jensen, Maribel Rodriguez-Torres, Lisa M Nyberg, Adrian M Di Bisceglie, Timothy R Morgan, Paul J Pockros, Amy Lin, Lisa Cupelli, Frank Duff, Ka Wang, David R Nelson
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 48 Issue 4 Pg. 1033-43 (Oct 2008) ISSN: 1527-3350 [Electronic] United States
• PMID: 18697207 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Adult
• Antiviral Agents (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Hepacivirus (genetics)
• Hepatitis C (blood, drug therapy)
• Humans
• Interferon alpha-2
• Interferon-alpha (adverse effects, therapeutic use)
• Middle Aged
• Pilot Projects
• Polyethylene Glycols (adverse effects, therapeutic use)
• RNA, Viral (blood)
• Recombinant Proteins
• Ribavirin (adverse effects, therapeutic use)
• Treatment Outcome