Department of Pediatrics, Helios Medical Center Wuppertal, Witten-Herdecke University, Germany.
Beijing 302 Hospital, Beijing, China.
The Royal Children's Hospital, Melbourne, VIC, Australia.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium.
First Affiliated Hospital of Kunming Medical College, Kunming, China.
Eighth People's Hospital of Guangzhou, Guangzhou, China.
LLC Medical Company 'Hepatolog', Samara, Russian Federation.
SouthWest Hospital, Third Military Medical University, Chongqing, China.
Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Roche (China) Holding Ltd, Shanghai, China.
Roche Pharma Research and Early Development, Roche Innovation Center, Basel, Switzerland.
Roche Products Limited, Welwyn Garden City, UK.
Children with chronic hepatitis B (CHB) represent an area of unmet medical need, due 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/cirrhosis were randomized (2:1) to PegIFN alfa-2a (Group A, n = 101) or no treatment (Group B, n = 50); patients with advanced fibrosis were assigned to PegIFN alfa-2a (Group C, n = 10). PegIFN alfa-2a was administered for 48 weeks by body surface area category, based on 180 µg/1.73m2 . HBeAg seroconversion rates at 24 weeks post-treatment were significantly higher in Group A (25.7% vs. 6%, P = 0.0043), as were the rates of Hepatitis B s 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.
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.