Pegylated Interferon +/- Ribavirin for Children with HCV (PEDS-C)

General Description

Treatment of chronic hepatitis C in adults has evolved from alpha interferon (IFNα) alone to the combination of PEG-IFNα with ribavirin (RV). Recommendations for treatment for HCV infection in children have been derived from trials in adults, although the efficacy and safety of these therapies may be different in children. The Pediatric Study of Hepatitis C (PEDS-C) was conducted as a randomized, controlled trial to investigate the safety and efficacy of PEG-IFNα with and without RV in children and adolescents with chronic hepatitis C. The primary objective of the PEDS-C study was to determine if the addition of RV to PEG-IFNα maximized outcome of therapy of children with chronic hepatitis C.

Children and adolescents ages 5 to 18 years with documented chronic HCV infection were enrolled in the study. All participants were randomly assigned in a 1:1 ratio to receive either PEG-IFNα and RV or PEG-IFNα and placebo. PEG-IFNα was administered in a dose of 180 µg/1.73m2 body surface area subcutaneously once weekly to all subjects, and ribavirin was administered in a dose of 15 mg/kg orally twice daily to the appropriate treatment group. Patients without detectable HCV RNA at 24 weeks were continued on treatment for another 24 weeks, while those with detectable HCV RNA at 24 weeks were considered treatment failures. The primary outcome measure was the proportion of subjects with a sustained virologic response, defined as non-detectable HCV RNA in plasma (<10 IU/ml) at least 24 weeks after stopping treatment. The secondary outcome measure was safety, assessed by vital signs, laboratory tests, and adverse events.

Results showed that therapy with PEG-IFNα plus RV was superior to PEG-IFNα plus placebo regardless of age, alanine aminotransferase (ALT) levels, and histologic severity. Additionally, there was little change in side effect profile with the addition of RV to PEG-IFNα. The study concluded that the combination of PEG-IFNα and RV is superior to PEG-IFNα alone as therapy for chronic hepatitis C in children and adolescents in both safety and efficacy.

Objectives

The primary objective of the PEDS-C study was to determine if the addition of RV to PEG-IFNα maximized outcome of therapy of children with chronic hepatitis C.

Outcome Measure

The primary outcome measure was the proportion of subjects with a sustained virologic response, defined as non-detectable HCV RNA in plasma (<10 IU/ml) at least 24 weeks after stopping treatment. The secondary outcome measure was safety, assessed by vital signs, laboratory tests, and adverse events.

Criteria

Children and adolescents ages 5 to 18 years who met the following criteria were eligible for enrollment:

• The presence of HCV RNA in plasma on 2 tests separated by at least 6 months
• Chronic liver disease, as indicated by inflammation and/or fibrosis, consistent with chronic hepatitis C infection on a liver biopsy obtained within the past 24 months
• Compensated liver disease (Child-Pugh Grade A clinical classification)
• Hemoglobin values > 11g/dL for females and > 12 g/dL for males
• Normal thyroid stimulating hormone (TSH)

Exclusion criteria are documented in the study protocol.

Outcome

Results showed that therapy with PEG-IFNα plus RV was superior to PEG-IFNα plus placebo regardless of age, alanine aminotransferase (ALT) levels, and histologic severity. Additionally, there was little change in side effect profile with the addition of RV to PEG-IFNα. The study concluded that the combination of PEG-IFNα and RV is superior to PEG-IFNα alone as therapy for chronic hepatitis C in children and adolescents in both safety and efficacy.