随机恩替卡韦与安慰剂的对照试验的儿童中HBeAg阳性慢性乙型

StephenW

Randomized Controlled Trial of Entecavir Versus Placebo in Children with HBeAg-positive Chronic Hepatitis B

    Maureen M. Jonas1,*, Mei-Hwei Chang2, Etienne Sokal3, Kathleen B. Schwarz4, Deirdre Kelly5, Kyung Mo Kim6, Simon C. Ling7, Philip Rosenthal8, Dumitru Oraseanu9, Laurie Reynolds10, Alexandra Thiry10 andPeter Ackerman10

DOI: 10.1002/hep.28015

© 2015 by the American Association for the Study of Liver Diseases

Issue
Cover image for Vol. 62 Issue 2
Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)
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    1    Boston Children's Hospital, Boston, MA
    2    National Taiwan University Hospital, Taipei, Taiwan
    3    Cliniques Universitaires St Luc, Université Catholique de Louvain, Brussels, Belgium
    4    Johns Hopkins Children's Center, Baltimore, MD
    5    Birmingham Children's Hospital, Birmingham, UK
    6    Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Republic of Korea
    7    The Hospital For Sick Children, and Department of Paediatrics, University of Toronto, Toronto, Canada
    8    University of California, San Francisco, CA
    9    Grigore Alexandrescu Emergency Hospital for Children, Bucharest, Romania
    10    Bristol-Myers Squibb, Wallingford, CT

*Corresponding author: Maureen M. Jonas, M.D, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA, Email: [email protected], Phone: 617-355-5837, Fax: 617-730-0716
Publication History

    Accepted manuscript online: 29 JUL 2015 07:49PM EST
    Manuscript Revised: 27 JUL 2015
    Manuscript Accepted: 27 JUL 2015
    Manuscript Received: 11 FEB 2015

Funded by

    Bristol-Myers Squibb


Keywords:

    hepatitis B virus;nucleos(t)ide analog treatment;child;adolescent;pediatric

Abstract

This ongoing, randomized phase III study assesses the safety and efficacy of entecavir versus placebo in nucleos(t)ide-naive children (2 to <18 years) with HBeAg-positive chronic hepatitis B (CHB). Blinded treatment was administered for a minimum of 48 weeks. After Week 48, patients with HBeAg seroconversion continued blinded treatment; those without, switched to open-label entecavir. The primary endpoint was HBeAg seroconversion and HBV DNA <50 IU/mL at Week 48. A total of 180 patients were randomized (2:1) and treated. Baseline median age was 12 years, with approximately 50% of children aged >12 to <18, and 25% each aged ≥2 to ≤6 and >6 to ≤12. Rates for the primary endpoint at Week 48 were significantly higher with entecavir than placebo (24.2% [29/120] versus 3.3% [2/60]; P=0.0008). Furthermore, higher response rates were observed with entecavir compared with placebo for the key Week 48 secondary endpoints: HBV DNA <50 IU/mL (49.2% [59/120] versus 3.3% [2/60]; P < 0.0001), alanine aminotransferase normalization (67.5% [81/120] versus 23.3% [14/60]; P < 0.0001), and HBeAg seroconversion (24.2% [29/120] versus 10.0% [6/60]; P = 0.0210). Among entecavir-randomized patients there was an increase in all efficacy endpoints between Weeks 48 and 96, including an increase from 49% to 64% in virologic suppression. The cumulative probability of emergent entecavir resistance through Years 1 and 2 of entecavir was 0.6 and 2.6%, respectively. Entecavir was well tolerated with no observed differences in adverse events or changes in growth compared with placebo. Conclusion: In childhood CHB, entecavir demonstrated superior antiviral efficacy to placebo with a favorable safety profile. These results support the use of entecavir as a therapeutic option in children and adolescents with CHB. This article is protected by copyright. All rights reserved.

StephenW

随机恩替卡韦与安慰剂的对照试验的儿童中HBeAg阳性慢性乙型肝炎

    莫林M. Jonas1，*，美Hwei长2，艾蒂安Sokal3，凯瑟琳B. Schwarz4，迪尔德丽Kelly5，莫炅Kim6，西蒙C. Ling7，菲利普Rosenthal8，杜米特鲁Oraseanu9，劳瑞Reynolds10，亚历山德拉Thiry10 andPeter Ackerman10

DOI：10.1002 / hep.28015

©2015年肝病研究的美国协会

问题
封面图片卷。 62第2期
肝病

接受第（接受，未编辑的文章，并在网上公布可引用的最终编辑和记录的排版本将出现在未来。）
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    1波士顿儿童医院，马萨诸塞州波士顿
    2台大医院，台北，台湾
    15-9诊所3圣Universitaires吕克，鲁汶天主教大学，布鲁塞尔，比利时
    4约翰斯·霍普金斯儿童中心，马里兰州巴尔的摩
    5伯明翰儿童医院，英国伯明翰
    6峨山医学中心儿童医院，蔚山医学院，首尔，韩国的大学
    7病童医院，儿科和多伦多大学，加拿大多伦多部
    加利福尼亚州，旧金山，加利福尼亚大学8
    9格里戈里Alexandrescu的应急儿童医院，布加勒斯特，罗马尼亚
    10百时美施贵宝，沃灵福德，CT

*通讯作者：莫林M.乔纳斯博士，波士顿儿童医院，300朗伍德大道，波士顿，MA 0​​2115，USA，电子邮件：[email protected]，电话：617-355-5837，传真：617- 730-0716
出版物历史

    接受稿件在线：2015年7月29日下午7时49 EST
    手稿修订：2015年7月27日
    稿件接受：2015年7月27日
    收稿：2015年2月11日

受资助

    施贵宝


关键词：

    乙肝病毒;核苷（酸）类似物IDE治疗;儿童，青少年;小儿

抽象

这种持续的，随机III期研究评估HBeAg阳性慢性乙型肝炎（CHB）的核苷（酸）IDE-天真的孩子的安全和恩替卡韦与安慰剂疗效（2〜<18岁）。盲治疗给药最少48周。 48周后，患者出现HBeAg血清学转换继续蒙蔽处理;那些没有，切换到开放标签恩替卡韦。主要终点是HBeAg血清转换和HBV DNA <50 IU / mL的在48周共180例患者随机（2：1），并处理。基线平均年龄为12岁，年龄> 12至<18的儿童的约50％，和25％的各年龄≥2至≤6和> 6至≤12。价格在48周的主要终点是显著高于恩替卡韦比安慰剂（24.2％[一百二十分之二十九]与3.3％[2/60]; P = 0.0008）。此外，更高的响应率，观察恩替卡韦与安慰剂的键第48周次级端点相比：HBV DNA <50IU /毫升（49.2％[59/120]对3.3％[2/60]，P <0.0001），丙氨酸转氨酶正常化（67.5％[一百二十○分之八十一]与23.3％[14/60]; P <0.0001），HBeAg血清转换（24.2％[120分之29]与10.0％[6/60]; P = 0.0210）。在恩替卡韦随机患者有增加的48周和96，包括增加49％至64％病毒学抑制之间的所有疗效终点。累积的紧急恩替卡韦耐药通过多年的1和2恩替卡韦的概率为0.6和2.6％，分别为。恩替卡韦耐受性好，不良事件或与安慰剂相比变化生长没有差异。结论：在慢性乙型肝炎的童年，恩替卡韦表现出卓越的抗病毒疗效与安慰剂一个良好的安全性。这些结果支持使用恩替卡韦在儿童和青少年慢性乙型肝炎患者的治疗选择。这篇文章是受版权保护的。版权所有。