Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B: The PEG-B-ACTIVE Study.

Abstract

Children with chronic hepatitis B (CHB) represent an area of unmet medical need, attributed to increased lifetime risk of CHB sequelae and limited therapeutic options compared with adult CHB patients. The PEG-B-ACTIVE (NCT01519960) phase III study evaluated peginterferon (PegIFN) alfa-2a treatment in children aged 3 to <18 years with CHB. A total of 161 hepatitis B e antigen (HBeAg)-positive immune-active patients without advanced fibrosis (AF)/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with AF were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area (BSA) category, based on 180 μg/1.73 m2 . HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in Group A (25.7% vs. 6%; P = 0.0043), as were the rates of hepatitis B surface antigen (HBsAg) clearance (8.9% vs. 0%; P = 0.03), hepatitis B virus (HBV) DNA <2,000 IU/mL (28.7% vs. 2.0%; P < 0.001) or undetectable (16.8% vs. 2.0%; P = 0.0069), and alanine aminotransferase (ALT) normalization (51.5% vs. 12%; P < 0.001). Safety, including incidence of ALT flares and neutropenia, was comparable to the established PegIFN alfa-2a profile in HBV-infected adults or hepatitis C virus-infected children. Changes in growth parameters were minimal during treatment and comparable to those in untreated patients. Safety and efficacy outcomes in Group C were in line with Group A. Conclusion: PegIFN alfa-2a treatment of children in the immune-active phase of CHB was efficacious and well tolerated, and associated with higher incidence of HBsAg clearance than in adults. This represents an important advance to the treatment options for children with CHB.

• Authors: Stefan Wirth, Hongfei Zhang, Winita Hardikar, Kathleen B Schwarz, Etienne Sokal, Weibo Yang, Huimin Fan, Vyacheslav Morozov, Qing Mao, Hong Deng, Yang Huang, Lei Yang, Nicolas Frey, Clare Nasmyth-Miller, Vedran Pavlovic, Cynthia Wat
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 68 Issue 5 Pg. 1681-1694 (11 2018) ISSN: 1527-3350 [Electronic] United States
• PMID: 29689122 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the American Association for the Study of Liver Diseases.

Chemical References

• Antiviral Agents
• DNA, Viral
• Hepatitis B e Antigens
• Interferon-alpha
• Recombinant Proteins
• Polyethylene Glycols
• peginterferon alfa-2a

Topics

• Adolescent
• Antiviral Agents (adverse effects, therapeutic use)
• Child
• Child, Preschool
• DNA, Viral (drug effects)
• Female
• Hepatitis B e Antigens
• Hepatitis B virus
• Hepatitis B, Chronic (drug therapy)
• Humans
• Interferon-alpha (adverse effects, therapeutic use)
• Male
• Polyethylene Glycols (adverse effects, therapeutic use)
• Recombinant Proteins (adverse effects, therapeutic use)
• Seroconversion (drug effects)
• Treatment Outcome