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A randomized, prospective trial of ribavirin 400 mg/day versus 800 mg/day in combination with peginterferon alfa-2a in hepatitis C virus genotypes 2 and 3
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Hepatology June 2008
Peter Ferenci 1 *, Harald Brunner 2, Hermann Laferl 3, Thomas-Matthias Scherzer 1, Andreas Maieron 4, Michael Strasser 5, Gabriele Fischer 6, Harald Hofer 1, Martin Bischof 7, Rudolf Stauber 8, Michael Gschwantler 9, Petra Steindl-Munda 1, Katharina Staufer 1, Karin Loschenberger 10, Austrian Hepatitis Study Group
1Department of Internal Medicine III, Medical University, Vienna, Austria
2Department of Internal Medicine 1, Hospital Hietzing, Vienna, Austria
3Department of Internal Medicine, Kaiser-Franz-Josef-Spital, Vienna, Austria
4Department of Internal Medicine, Elisabethinen Hospital, Linz, Austria
5Department of Internal Medicine I, St. Josef Hospital, Salzburg, Austria
6Department of Psychiatry, Medical University, Vienna, Austria
7Department of Internal Medicine IV, Rudolfsspital, Vienna, Austria
8Department of Internal Medicine, Medical University, Graz, Austria
9Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria
10Roche Austria, Vienna, Austria
Potential conflict of interest: Dr. Gschwantler is on the speakers' bureau of and received grants from Hoffmann-La Roche. Dr. Staufer is on the speakers' bureau of and received grants from Roche. Dr. Laferl received grants from Roche. Dr. Ferenci is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche.
Abstract
We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day (group A) or 400 mg/day (group B) plus peginterferon alfa-2a 180 ug/week in treatment-naive patients infected with hepatitis C virus (HCV) genotype 2 or 3.
A total of 97 of 141 patients randomized to group A (68.8%, 95% confidence interval [CI] 60.5%-76.3%) and 90 of 141 patients randomized to group B (63.8; 95% CI 55.3%-71.7%) achieved a sustained virological response, defined as undetectable serum HCV RNA at the end of untreated follow-up (week 48).
Among patients infected with genotype 3, the rate of sustained virological response was 67.5% (95% CI 58.4%-75.6%) in group A and 63.9% (95% CI 54.7%-72.4%) in group B, and among patients infected with genotype 2, the rate of sustained virological response was 77.8% (95% CI 54.2%-93.6%) in group A and 55.6% (95% CI 38.4%-83.7%) in group B.
Relapse rates in the 2 treatment groups were similar (17% in group A and 20% in group B).
The incidence of adverse events, laboratory abnormalities, and dose reductions was similar in the 2 treatment groups.
Conclusion: The results suggest that when administered for 24 weeks with peginterferon alfa-2a, ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3.
The prevalence of chronic infection with hepatitis C virus (HCV) is estimated to range from 1.5% to 15% depending on the region. In Europe, 8 million to 10 million individuals suffer from chronic hepatitis C, and it is expected that over 10 to 20 years, approximately 20% of these individuals will develop cirrhosis and its complications and will be in need of liver transplantation.[1][2]
Effective treatment for chronic hepatitis C would reduce morbidity and mortality, improve health-related quality of life, and avoid the huge costs associated with end-stage liver disease. The current standard of care is a combination of pegylated interferon and ribavirin, which produces an overall cure rate of approximately 50% to 60%.[3][4]
The most important predictor of successful response to combination therapy is HCV genotype.[5] On the basis of a large randomized international study,[4] the optimum treatment for patients with HCV genotype 1 infection is considered to be 48 weeks of combination therapy with pegylated interferon plus ribavirin 1000 or 1200 mg/day.[5] In contrast, patients infected with HCV genotype 2 or 3 may be treated with a lower dose of ribavirin (800 mg/day) and for just 24 weeks without compromising efficacy.[6][7] These findings are reflected in treatment guidelines for chronic hepatitis C.[5]
The use of a lower, fixed 800 mg/day dose of ribavirin is better tolerated and as effective as the higher 1000 or 1200 mg/day standard dose of ribavirin in patients infected with HCV genotype 2 or 3. Recent attempts to further simplify treatment for these patients have focused on shortening the duration to 12 to 16 weeks,[8-11] but it is now clear that abbreviated regimens result in higher relapse rates when compared with the standard 24-week regimen.[10] It remains to be determined whether the tolerability of treatment can be improved and the costs reduced by further decreasing the dose of ribavirin. For this reason, we compared the efficacy and tolerability of 24 weeks of treatment with ribavirin at a dosage of 800 or 400 mg/day in combination with peginterferon alfa-2a in patients infected with HCV genotype 2 or 3.
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