High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin

Background & Aims

Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children.

Methods

Children and adolescents ages 3–17 years were treated with PEG-IFN alfa-2b (60 μg/m²/week) plus RBV (15 mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000 IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (⩾600,000 IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy.

Results

SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported.

Conclusion

Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

Introduction

Pegylated interferon (PEG-IFN) alfa in combination with ribavirin (RBV) is standard of care for adults with chronic hepatitis C (CHC). Recently, PEG-IFN alfa-2b in combination with RBV was approved in the US for children age 3 years and older [1]. The main advantage of PEG-IFN alfa is the extended serum half-life conferred by pegylation of the IFN molecule, which permits a once-weekly administration regimen with improved efficacy and a safety profile similar to that of IFN alfa [2], [3]. To date, studies of PEG-IFN alfa in children and adolescents have been limited to a few pilot studies with small patient numbers and non-standardized treatment regimens [4], [5], [6].

In the US, the seroprevalence of hepatitis C virus infection is 0.2% among children and 0.4% among adolescents [7], and comparable or slightly lower prevalence data have been reported in Western Europe, South America, and Taiwan [8], [9], [10]. Because viral transmission from blood transfusion has been virtually eliminated in the past two decades, vertical infection is now responsible for most new cases of HCV infection among children in the Western world. Although progression of liver disease in children with CHC is slow, severe fibrosis and cirrhosis may develop in approximately 5% of infected children by the time they reach adulthood [11]. Thus, pediatric hepatitis C is an important health care issue, with associated costs in the US estimated between $17 and $40 million annually [12]. Effective early treatment of hepatitis C in children can prevent the long-term consequences of chronic infection, improving patient prognosis and reducing health care expenditures.

Previous studies suggest that children treated with conventional IFN alfa or PEG-IFN alfa combined with RBV attain SVR rates similar to or better than those of adults [4], [6]. Treatment should be considered for children with CHC because it provides high response rates with improved tolerability, alleviating the long-term sequelae and psychological burden of the disease.

The aim of this study was to evaluate the efficacy, tolerability, and pharmacokinetics of treatment with PEG-IFN alfa-2b plus RBV in children with CHC.