Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics

Regino P. González-Peralta, Deirdre A. Kelly, Barbara Haber, Jean Molleston, Karen F. Murray, Maureen M. Jonas, Mark Shelton, Giorgina Mieli-Vergani, Yoav Lurie, Steven Martin, Thomas Lang, Andrew Baczkowski, Michael Geffner, Samir Gupta, Mark Laughlin

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Abstract

Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalHepatology
Volume42
Issue number5
DOIs
StatePublished - Nov 1 2005

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interferon alfa-2b
Ribavirin
Chronic Hepatitis C
Hepacivirus
Pharmacokinetics
Safety
Therapeutics
Genotype
RNA
Virus Diseases
Serum
Area Under Curve
Liver Diseases

ASJC Scopus subject areas

  • Hepatology

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Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children : Efficacy, safety, and pharmacokinetics. / González-Peralta, Regino P.; Kelly, Deirdre A.; Haber, Barbara; Molleston, Jean; Murray, Karen F.; Jonas, Maureen M.; Shelton, Mark; Mieli-Vergani, Giorgina; Lurie, Yoav; Martin, Steven; Lang, Thomas; Baczkowski, Andrew; Geffner, Michael; Gupta, Samir; Laughlin, Mark.

In: Hepatology, Vol. 42, No. 5, 01.11.2005, p. 1010-1018.

Research output: Contribution to journalArticle

González-Peralta, RP, Kelly, DA, Haber, B, Molleston, J, Murray, KF, Jonas, MM, Shelton, M, Mieli-Vergani, G, Lurie, Y, Martin, S, Lang, T, Baczkowski, A, Geffner, M, Gupta, S & Laughlin, M 2005, 'Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: Efficacy, safety, and pharmacokinetics', Hepatology, vol. 42, no. 5, pp. 1010-1018. https://doi.org/10.1002/hep.20884
González-Peralta, Regino P. ; Kelly, Deirdre A. ; Haber, Barbara ; Molleston, Jean ; Murray, Karen F. ; Jonas, Maureen M. ; Shelton, Mark ; Mieli-Vergani, Giorgina ; Lurie, Yoav ; Martin, Steven ; Lang, Thomas ; Baczkowski, Andrew ; Geffner, Michael ; Gupta, Samir ; Laughlin, Mark. / Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children : Efficacy, safety, and pharmacokinetics. In: Hepatology. 2005 ; Vol. 42, No. 5. pp. 1010-1018.
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T1 - Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children

T2 - Efficacy, safety, and pharmacokinetics

AU - González-Peralta, Regino P.

AU - Kelly, Deirdre A.

AU - Haber, Barbara

AU - Molleston, Jean

AU - Murray, Karen F.

AU - Jonas, Maureen M.

AU - Shelton, Mark

AU - Mieli-Vergani, Giorgina

AU - Lurie, Yoav

AU - Martin, Steven

AU - Lang, Thomas

AU - Baczkowski, Andrew

AU - Geffner, Michael

AU - Gupta, Samir

AU - Laughlin, Mark

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N2 - Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus.

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