TY - JOUR
T1 - Efficacy and Safety of Peginterferon Alfa-2a (40KD) in Children With Chronic Hepatitis B
T2 - The PEG-B-ACTIVE Study
AU - Wirth, Stefan
AU - Zhang, Hongfei
AU - Hardikar, Winita
AU - Schwarz, Kathleen B.
AU - Sokal, Etienne
AU - Yang, Weibo
AU - Fan, Huimin
AU - Morozov, Vyacheslav
AU - Mao, Qing
AU - Deng, Hong
AU - Huang, Yang
AU - Yang, Lei
AU - Frey, Nicolas
AU - Nasmyth-Miller, Clare
AU - Pavlovic, Vedran
AU - Wat, Cynthia
N1 - Funding Information:
The authors thank the patients, their families, and the study investigators who took part in this study. In addition to the authors, the following investigators participated in the study: Yuriy Antipkin, Sanjay Bansal, Valentyna Berezenko, Xin Yue Chen, Ruth De Bruyne, Feng Fang, Zhi Liang Gao, Miglena Georgieva, Anna Gorczyca, Evelyn Hsu, Maureen Jonas, Deirdre Kelly, Sergiy Kramarov, Daniel Leung, Shumei Lin, Yuri Lobzin, Ewa Majda-Stanislawska, Giorgina Mielei-Vergani, David Moore, Assy Nimer, Malgorzata Pawlowska, Alexander Potapov, Rifaat Safadi, Ron Shaoul, Tatiania Strokova, Gabriella Verucchi, Xiaozhong Wang, Zhaoxia Wang, Gareth Tudor-Williams, and Christo Zhelev. Support for third-party writing assistance, furnished by John Carron, Ph.D., of Health Interactions, was provided by Roche Products Ltd, Welwyn Garden City, UK.
Funding Information:
Received September 1, 2017; accepted April 18, 2018. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.30050/suppinfo. Supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. *Stefan Wirth and Hongfei Zhang are joint first authors. © 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30050 Potential conflict of interest: Dr. Nasmyth-Miller is employed by Roche. Dr. Wat is employed by and owns stock in Roche. Dr. Wirth consults for Roche. Dr. Pavlovic is employed by Roche. Dr. Sokal consults for, advises for, received grants from, and owns stock in Promethera. Dr. Schwarz consults for, advises for, and received grants from Gilead. She consults for and received grants from Roche. She consults for UpToDate. She received grants from Bristol-Myers Squibb. Dr. Huang is employed by Roche. Dr. Frey is employed and owns stock in F. Hoffmann-La Roche.
Publisher Copyright:
© 2018 by the American Association for the Study of Liver Diseases.
PY - 2018/11
Y1 - 2018/11
N2 - 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 m 2 . 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.
AB - 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 m 2 . 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.
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U2 - 10.1002/hep.30050
DO - 10.1002/hep.30050
M3 - Article
C2 - 29689122
AN - SCOPUS:85053736220
SN - 0270-9139
VL - 68
SP - 1681
EP - 1694
JO - Hepatology
JF - Hepatology
IS - 5
ER -