Clinical Advances in Liver, Pancreas, and Biliary TractThe Combination of Ribavirin and Peginterferon Is Superior to Peginterferon and Placebo for Children and Adolescents With Chronic Hepatitis C
Section snippets
Subjects
Subjects were enrolled by the investigators at each site from December 2004 to May 2006 at 11 US medical centers (www.ClinicalTrials.gov). The study was completed as per the original design, with 2 years of off-therapy follow-up. The last patient completed the 2-year follow-up in February 2010. Inclusion criteria included age 5 to 18 years with chronic HCV infection documented by the presence of HCV RNA in plasma on 2 occasions at least 6 months apart and chronic liver disease as indicated by
Subject Characteristics
Supplementary Figure 1 shows the number of children randomized, treated, and followed up. Baseline characteristics were similar in the 2 treatment groups (Table 1). Most children had early-stage disease; only 5 (4%) had bridging fibrosis and 1 (2%) had cirrhosis.24
Treatment Responses
The primary end point, an SVR, was met by 29 children (53%; 95% confidence interval [CI], 40%–66%) in the PEG-2a plus RV group compared with only 12 (21%; 95% CI, 10%–32%) in the PEG-2a plus placebo group (P < .001). HCV RNA levels
Discussion
This prospective, randomized, controlled trial has shown that the addition of RV to PEG alfa-2a significantly increases early as well as sustained response rates. Therapy with PEG-2a plus RV was superior to PEG-2a plus placebo regardless of age, alanine aminotransferase levels, and degree of histologic severity. The single exception to the superiority of combination therapy was in the small group of children with HCV RNA levels <600,000 IU/mL who responded well regardless of whether RV was
Acknowledgments
The authors thank the following individuals, who were instrumental in the planning, administration, or care of patients enrolled in this study from all participating institutions: Jay H. Hoofnagle, MD, director, Liver Disease Research Branch, scientific advisor, Edward Doo, MD, scientific advisor, and Rebecca Torrance, RN, administrative assistant, National Institute of Diabetes and Digestive and Kidney Diseases; Beth Garrett, RN, study coordinator, and Kathleen M. Brown PhD, study manager,
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2020, Advances in PediatricsCitation Excerpt :Ribavirin, a guanosine analog, interrupts viral RNA synthesis by interfering with HCV RNA polymerase. Ribavirin is added to IFN-alpha treatment to increase the sustained virologic response (SVR) and decrease the rate of relapse and development of viral resistance [29]. Not only is Peg-IFN a weekly injection, but the combined treatment regimen of Peg-IFN and ribavirin had multiple adverse effects, including fever, headache, gastrointestinal symptoms, depression, neutropenia, hemolytic anemia, and growth suppression.
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2020, Journal of PediatricsCitation Excerpt :To appreciate the degree of superiority of DAA therapy over previous older HCV regimens, a review of historical antiviral therapeutic strategies, including PEG-IFN/RBV, is warranted. Although sustained viral response (SVR) rates improved over time from ∼16% with IFN monotherapy to >50% with the combination of RBV and PEG-IFN, these SVR rates were frustratingly low.4-22 Further complicating the use of RBV plus PEG-IFN treatment were the prolonged treatment duration (48 weeks), the intensive on-therapy monitoring required, and the known side effect profiles.
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2019, The Lancet Gastroenterology and HepatologyCitation Excerpt :The only approved treatment for children younger than 12 years is 24–48 weekly injections of peginterferon alfa-2a or peginterferon alfa-2b with twice-daily ribavirin, according to the HCV genotype (24 weeks for genotypes 2 and 3, and 48 weeks for genotypes 1 and 4).81 Overall, 11 clinical trials (one randomised and ten open-label, non-randomised) have been done on the use of peginterferon alfa in adolescents and children younger than 12 years.91–101 In genotype 1 HCV, the SVR12 of peginterferon alfa and ribavirin was worse than that for the direct-acting antiviral, with an SVR12 of only 52% in those with HCV genotype 1 and 4, and 89% in genotypes 2 and 3.81,102
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Conflicts of interest The authors disclose the following: Dr Schwarz is supported by Roche (grant/research support), Bristol-Myers Squibb (grant/research support), Gilead (grant/research support), and Novartis (consultant). Dr Gonzalez-Peralta is supported by Boehringer-Ingelheim (grant/research support), Roche (grant/research support), Bristol Myers-Squibb (grant/research support), and Novartis (consultant). Dr Murray is supported by Roche (grant/research support), Bristol-Myers Squibb (grant/research support), and Novartis. Dr Molleston, Dr Haber, Dr Jonas, Dr Rosenthal, Dr Smith, Dr Lobritto, and Dr Valsamakis are supported by Roche (grant/research support). Dr Mohan is supported by Roche (grant/research support) and Gilead (grant/research support). Dr Balistreri is supported by Digestive Care Inc (consultant) and Roche (grant/research support). Dr Narkewicz is supported by Novartis (consultant) and Roche (grant/research support). Dr Rossi is an employee of Roche Molecular Systems. The remaining authors disclose no conflicts.
Funding Supported by a cooperative agreement between the National Institute of Diabetes and Digestive and Kidney Diseases and the Food and Drug Administration (contract no. 1UO1DK067767-01.CRC) and in part by National Institutes of Health/National Center for Research Resources Colorado CTSI grant no. UL1 RR025780 and the following study sites: M01-RR-00069, Children's Hospital, Aurora, CO; M01-RR-02172, Children's Hospital Boston, Boston, MA; M01-RR-01271, University of California, San Francisco, CA; 5-M01-RR-020359-01, Children's National Medical Center, Washington, DC; M01-RR-00645, Columbia University Medical Center, New York, NY; M01-RR-00082, University of Florida, Gainesville, FL; M01-RR-00037, University of Washington, Seattle, WA; 5-M01-RR-000240, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA; U01-DK-067767-02, Johns Hopkins Medical Center, Baltimore, MD; M01-RR-08084, University of Cincinnati, Cincinnati, OH; and M01-RR-00750, Indiana University, Indianapolis, IN. The contents of this report are the authors' sole responsibility and do not necessarily represent the official views of the National Institutes of Health. Additional support was provided by Hoffmann-La Roche for study medications, the data coordinating center, and central laboratory costs.