Viral Hepatitis

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Improved outcomes in patients with hepatitis C with difficult-to-treat characteristics: Randomized study of higher doses of peginterferon α-2a and ribavirin†

  1. Michael W. Fried1,*,‡,
  2. Donald M. Jensen2,
  3. Maribel Rodriguez-Torres3,
  4. Lisa M. Nyberg4,
  5. Adrian M. Di Bisceglie5,
  6. Timothy R. Morgan6,
  7. Paul J. Pockros7,
  8. Amy Lin8,
  9. Lisa Cupelli8,
  10. Frank Duff8,
  11. Ka Wang8,
  12. David R. Nelson9

Article first published online: 9 JUN 2008

DOI: 10.1002/hep.22448

Issue

Hepatology

Hepatology

Volume 48, Issue 4, pages 1033–1043, October 2008

Additional Information

How to Cite

Fried, M. W., Jensen, D. M., Rodriguez-Torres, M., Nyberg, L. M., Di Bisceglie, A. M., Morgan, T. R., Pockros, P. J., Lin, A., Cupelli, L., Duff, F., Wang, K. and Nelson, D. R. (2008), Improved outcomes in patients with hepatitis C with difficult-to-treat characteristics: Randomized study of higher doses of peginterferon α-2a and ribavirin. Hepatology, 48: 1033–1043. doi: 10.1002/hep.22448

Author Information

  1. 1

    University of North Carolina, Chapel Hill, NC

  2. 2

    University of Chicago Chicago IL

  3. 3

    Fundacion de Investigacion De Diego Santurce Puerto Rico

  4. 4

    Kaiser Permanente Medical Center San Diego CA

  5. 5

    St. Louis University St. Louis MO

  6. 6

    Veterans Affairs Medical Center Long Beach CA

  7. 7

    Scripps Clinic La Jolla CA

  8. 8

    Roche Nutley NJ

  9. 9

    University of Florida Gainesville FL

*Correspondence: Michael W. Fried, University of North Carolina, CB 7584, Room 8015 Burnett Womack Building, Chapel Hill, NC 27514

  1. †

    Potential conflict of interest: Dr. Fried advises Roche. Dr. Jensen is a consultant and advises Roche. Dr. Rodriguez-Torres is on the speakers' bureau of, is a consultant for, and received grants from Roche. She received grants from Anadys Pharmaceuticals, Astra Zeneca, Bristol-Myers Squibb, Human Genome Sciences, Intermune, Pharmassett, Sciclone Pharmaceuticals, Valeant Pharmaceuticals, Vertex Pharmaceuticals, Virochem Pharma, and Wyeth Pharmaceuticals. She is a consultant for and received grants from GlaxoSmithKline and Idenix/Novartis Pharmaceuticals. She is also a consultant for Abbott Pharmaceuticals. Dr. Nyberg received grrants from Roche, Novartis, Human Genome, Bristol-Myers Squibb, and Vertex Pharmaceuticals. She is on the speakers' bureau of and received grants from Schering-Plough. Dr. DiBisceglie is a consultant for, advises, is on the speakers' bureau of, and received grants from Roche. Dr. Morgan is a consultant for, is on the speakers' bureau of, and received grants from Hoffmann-La Roche. Dr. Pockros is a consultant for, is on the speakers' bureau of, and received grants from Roche. Dr. Nelson advises, is on the speakers' bureau of, and received grants from Roche.

  2. ‡

    fax: 919-966-1700

Publication History

  1. Issue published online: 26 SEP 2008
  2. Article first published online: 9 JUN 2008
  3. Accepted manuscript online: 9 JUN 2008 12:00AM EST
  4. Manuscript Accepted: 20 MAY 2008
  5. Manuscript Received: 20 JUL 2007

Funded by

  • F. Hoffmann-La Roche
  • National Institutes of Health. Grant Numbers: GCRC RR 00046, K24 DK066144

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Abstract

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 μg/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 μg/week) the magnitude of HCV RNA reduction was significantly greater than for patients randomized to the conventional dose of peginterferon alfa-2a (180 μg/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 μg/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 μg/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. (HEPATOLOGY 2008.)

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