TY - JOUR
T1 - Safety, efficacy and pharmacokinetics of peginterferon α2a (40 kd) in children with chronic hepatitis C
AU - Schwarz, Kathleen B.
AU - Mohan, Parvathi
AU - Narkewicz, Michael R.
AU - Molleston, Jean Pappas
AU - Nash, S. Russell
AU - Hu, Sylvia
AU - Wang, Ka
AU - Gries, Jean Michel
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon α2a (pegINF-α2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m)/(1.73 m) × 180 μg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-α2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-α2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.
AB - Chronic hepatitis C virus (HCV) infection in children is a problem affecting thousands of children worldwide. Although standard interferon (INF) has better efficacy in pediatric patients than in adults, results in children with genotype 1 are poor; response rates to combination treatment with standard INF and ribavirin are better but the treatment requires thrice-weekly injections. The improved antiviral efficacy of weekly pegylated interferons relative to standard interferons in adults with chronic HCV infection suggests that pegylated interferons may also improve antiviral efficacy in children. We therefore investigated the pharmacokinetics, efficacy and safety of peginterferon α2a (pegINF-α2a) (40 kd) in 14 children ages 2 to 8 years with chronic hepatitis C (13 genotype 1, 1 non-1 genotype). Drug dose was calculated from each patient's body surface area (BSA) according to the formula BSA (m)/(1.73 m) × 180 μg, and patients were administered once-weekly subcutaneous injections for 48 weeks. Viral load and pharmacokinetic parameters were determined from blood drawn throughout the study and during follow-up. At week 24, the mean trough concentration was about 20% below values obtained from adults treated with pegINF-α2a, and the area under the curve from 0 to 168 hours was about 20% above adult values, suggesting that drug doses calculated from BSA achieved therapeutically adequate concentrations. Six of 14 patients (43%), all infected with genotype 1, achieved a sustained virological response. Adverse events were those commonly associated with INF-based treatment, and none was deemed serious. In conclusion, our findings provide a basis for larger studies evaluating the efficacy and safety of pegINF-α2a as monotherapy as well as in combination with ribavirin in pediatric patients with chronic hepatitis C.
KW - Body surface area
KW - HCV
KW - Monotherapy
KW - SVR
KW - Viral load
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U2 - 10.1097/01.mpg.0000235974.67496.e6
DO - 10.1097/01.mpg.0000235974.67496.e6
M3 - Article
C2 - 17033526
AN - SCOPUS:33749509615
SN - 0277-2116
VL - 43
SP - 499
EP - 505
JO - Journal of pediatric gastroenterology and nutrition
JF - Journal of pediatric gastroenterology and nutrition
IS - 4
ER -