title: Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: efficacy, safety, and pharmacokinetics.
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.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Florida, Gainesville, FL 32610, USA. regino@peds.ufl.edu
authors.forename: Regino P
authors.initials: RP
authors.lastname: González-Peralta
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Kelly
authors.forename: Barbara
authors.initials: B
authors.lastname: Haber
authors.forename: Jean
authors.initials: J
authors.lastname: Molleston
authors.forename: Karen F
authors.initials: KF
authors.lastname: Murray
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Jonas
authors.forename: Mark
authors.initials: M
authors.lastname: Shelton
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Yoav
authors.initials: Y
authors.lastname: Lurie
authors.forename: Steven
authors.initials: S
authors.lastname: Martin
authors.forename: Thomas
authors.initials: T
authors.lastname: Lang
authors.forename: Andrew
authors.initials: A
authors.lastname: Baczkowski
authors.forename: Michael
authors.initials: M
authors.lastname: Geffner
authors.forename: Samir
authors.initials: S
authors.lastname: Gupta
authors.forename: Mark
authors.initials: M
authors.lastname: Laughlin
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001827:Body Height / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin