The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C

Kathleen B Schwarz, Regino P Gonzalez-Peralta, Karen F Murray, Jean P Molleston, Barbara A Haber, Maureen M Jonas, Philip Rosenthal, Parvathi Mohan, William F Balistreri, Michael R Narkewicz, Lesley Smith, Steven J Lobritto, Stephen Rossi, Alexandra Valsamakis, Zachary Goodman, Patricia R Robuck, Bruce A Barton, Peds-C Clinical Research Network, Kathleen B Schwarz, Regino P Gonzalez-Peralta, Karen F Murray, Jean P Molleston, Barbara A Haber, Maureen M Jonas, Philip Rosenthal, Parvathi Mohan, William F Balistreri, Michael R Narkewicz, Lesley Smith, Steven J Lobritto, Stephen Rossi, Alexandra Valsamakis, Zachary Goodman, Patricia R Robuck, Bruce A Barton, Peds-C Clinical Research Network

Abstract

Background & aims: Although randomized trials of adults infected with hepatitis C virus (HCV) have shown that ribavirin increases the efficacy of pegylated interferon (PEG), such trials have not been performed in children. We conducted a randomized controlled trial of PEG and ribavirin, compared with PEG and placebo, in children 5 to 17 years old with chronic hepatitis C.

Methods: HCV RNA-positive children from 11 university medical centers were randomly assigned to receive either PEG alfa-2a (PEG-2a; 180 μg/1.73 m(2) body surface area, subcutaneously each week; n = 55) and ribavirin (15 mg/kg orally in 2 doses daily) or PEG-2a and placebo (n = 59) for 48 weeks. The primary end point was sustained virologic response (SVR; lack of detectable HCV RNA at least 24 weeks after stopping therapy).

Results: SVR was achieved in 53% of children treated with PEG-2a and ribavirin, compared with 21% of children who received PEG-2a and placebo (P < .001). Early virologic response (HCV RNA reduction >2 log(10) IU at 12 weeks) had a negative predictive value of only 0.89 in children with genotype 1, indicating that these children might benefit from 24 weeks of therapy before stopping treatment. Side effects, especially neutropenia, led to dose modification in 40% of children. Eighty-two percent of the PEG/ribavirin and 86% of the PEG/placebo group were in compliance with the year 2 follow-up visit; the durability of virologic response was 100% in both groups.

Conclusions: The combination of PEG and ribavirin is superior to PEG and placebo as therapy for chronic hepatitis C in children and adolescents.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
CONSORT Diagram Differences in n between Week 72 and n at the second annual visit = patients lost to follow up (total of 10 for PEG 2a plus RV and 8 for PEG 2a plus placebo.)
Figure 2
Figure 2
Mean Log10 HCV RNA levels during the first 24 weeks of treatment by time on study (weeks) and treatment group
Figure 3
Figure 3
Percent of patients with no detectable virus by time on study (weeks) and treatment group
Figure 4A
Figure 4A
White Blood Cells (WBC × 103/μL) by Time on Study (Weeks) and Treatment Group
Figure 4B
Figure 4B
Absolute Neutrophil Count (ANC × 103/μL) by Time on Study (Weeks) and Treatment Group

Source: PubMed

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