第四阶段随机临床研究：聚乙二醇干扰素α-2a联合阿德福韦

StephenW

J Formos Med Assoc. 2018 Feb 15. pii: S0929-6646(17)30716-7. doi: 10.1016/j.jfma.2017.12.007. [Epub ahead of print]
Phase IV randomized clinical study: Peginterferon alfa-2a with adefovir or entecavir pre-therapy for HBeAg-positive chronic hepatitis B.Hsu CW1, Su WW2, Lee CM3, Peng CY4, Chuang WL5, Kao JH6, Chu HC7, Huang YH8, Chien RN9, Liaw YF10.
Author information
1Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan.2Changhua Christian Hospital, Department of Internal Medicine, Changhua, Taiwan.3Chang Gung Memorial Hospital-Kaohsiung, Chang Gung University College of Medicine, Kaohsiung, Taiwan.4China Medical University Hospital, Department of Hepato-Gastroenterology, Taichung, Taiwan.5Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.6National Taiwan University Hospital, Department of Hepato-Gastroenterology, Taipei, Taiwan.7Tri-Service Hospital, Department of Internal Medicine, Taipei, Taiwan.8Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.9Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: [email protected].10Liver Research Unit, Chang Gung Memorial Hospital-LinKou, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address: [email protected].

AbstractBACKGROUND: Efficacy of sequential therapy with nucleos(t)ide analogues and interferons versus monotherapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) remains unexplored. We aimed to assess efficacy and safety of sequential therapy with adefovir (ADV) or entecavir (ETV) followed by peginterferon (PEG-IFN) alfa-2a in Taiwanese patients with HBeAg-positive.
METHODS: This randomized, placebo-controlled, double-blind trial was conducted at nine sites in Taiwan from April 2010 to October 2013. Patients (N = 280) were randomized 1:1:1 to receive placebo, ETV or ADV alone for four weeks, combined with PEG-IFN alfa-2a for two weeks, then PEG-IFN alfa-2a alone for 46 weeks. The primary efficacy end point was HBeAg seroconversion at 48 weeks post-treatment.
RESULTS: No significant differences were observed among groups for HBeAg seroconversion (PEG-IFN alfa-2a+placebo, 36.3%; PEG-IFN alfa-2a+ETV, 29.5%; and PEG-IFN alfa-2a+ADV, 27.4%), HBeAg loss (37.4%, 32.2%, and 28.6%, respectively) or change in hepatitis B surface antigen (HBsAg) levels from baseline (-0.56 IU/mL, -0.60 IU/mL, and -0.41 IU/mL, respectively). However, hepatitis B virus DNA levels were higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa+ETV at week 64 (p = 0.0412), 76 (p = 0.0311), and 88 (p = 0.0113), and alanine aminotransferase (ALT) normalization rate was higher with PEG-IFN alfa-2a+placebo than PEG-IFN alfa-2a+ADV (p = 0.0283) or PEG-IFN alfa-2a+ETV (p = 0.0369) at week 88. Sub-analysis of results revealed an association between on-treatment HBsAg and ALT levels and efficacy 48 weeks post-treatment. Safety was comparable among treatment groups.
CONCLUSION: Pre-therapy with ADV or ETV followed by PEG-IFN alfa-2a is not superior to PEG-IFN alfa-2a monotherapy in Taiwanese patients with HBeAg-positive CHB.
CLINICAL TRIAL ID: NCT: 00922207.

Copyright © 2018. Published by Elsevier B.V.

KEYWORDS: Adefovir; Chronic hepatitis B; Entecavir; Hepatitis B e antigen; Peginterferon alfa-2a

PMID:29456079DOI:10.1016/j.jfma.2017.12.007

StephenW

J Formos Med Assoc。 2018年2月15日。pii：S0929-6646（17）30716-7。 doi：10.1016 / j.jfma.2017.12.007。 [电子版提前打印]
第四阶段随机临床研究：聚乙二醇干扰素α-2a联合阿德福韦或恩替卡韦预先治疗HBeAg阳性慢性乙型肝炎。
Hsu CW1，Su WW2，Lee CM3，Peng CY4，Chuang WL5，Kao JH6，Chu HC7，Huang YH8，Chien RN9，Liaw YF10。
作者信息

1
    台湾桃园长庚大学医学院临口长庚医院肝脏研究室。
2
    彰化基督教医院，台湾彰化内科。
3
    台湾高雄长庚大学医学院高雄长庚医院。
4
    中国医科大学附属医院台湾台中市肝胃病科。
五
    高雄医科大学高雄医科大学附属医院高雄，台湾。
6
    台湾台北大学附属医院肝肠消化科。
7
    台湾台北内科医院三院。
8
    国立阳明大学临床医学研究所台北退伍军人医院消化科和肝病科，台湾台北。
9
    台湾桃园长庚大学医学院临口长庚医院肝脏研究室。电子地址：[email protected]。
10
    台湾桃园长庚大学医学院临口长庚医院肝脏研究室。电子地址：[email protected]。

抽象
背景：

核苷（酸）类似物和干扰素序贯疗法与单药治疗乙型肝炎e抗原（HBeAg）阳性慢性乙型肝炎（CHB）患者的疗效仍未探索。我们旨在评估在HBeAg阳性的台湾患者中使用阿德福韦酯（ADV）或恩替卡韦（ETV）和聚乙二醇干扰素（PEG-IFN）alfa-2a进行顺序治疗的有效性和安全性。
方法：

这项随机，安慰剂对照双盲试验于2010年4月至2013年10月在台湾的9个地点进行。患者（N = 280）随机分配1：1：1接受安慰剂，ETV或ADV单独4周，联合PEG-IFNα-2a两周，然后单独PEG-IFNα-2a共46周。主要疗效终点是治疗后48周的HBeAg血清学转换。
结果：

HBeAg血清学转换（PEG-IFNα-2a +安慰剂，36.3％; PEG-IFNα-2a + ETV，29.5％; PEG-IFNα-2a + ADV，27.4％），HBeAg血清学转换（分别为-0.56 IU / mL，-0.60 IU / mL和-0.41 IU / mL）的乙型肝炎表面抗原（HBsAg）水平下降（分别为37.4％，32.2％和28.6％）或变化。然而，在第64周（p = 0.0412），76（p = 0.0311）和88（p = 0.0113），PEG-IFNα-2a +安慰剂的乙肝病毒DNA水平高于PEG-IFNα+ ETV在第88周时，PEG-IFNα-2a +安慰剂的丙氨酸转氨酶（ALT）归一化率高于PEG-IFNα-2a + ADV（p = 0.0283）或PEG-IFNα-2a + ETV（p = 0.0369）。结果的次分析揭示治疗后48周治疗中HBsAg和ALT水平与疗效之间的关联。治疗组之间安全性相当。
结论：

在HBeAg阳性慢性乙型肝炎患者中，使用ADV或ETV治疗，然后使用PEG-IFN alfa-2a治疗并不优于PEG-IFNα-2a单药治疗。
临床试用版ID：

NCT：00922207。

版权所有©2018. Elsevier B.V.
关键词：

阿德福韦;慢性乙型肝炎;恩替卡韦;乙型肝炎e抗原;聚乙二醇干扰素α-2a

结论：
    29456079
DOI：
    10.1016 / j.jfma.2017.12.007

StephenW

http://www.jfma-online.com/article/S0929-6646(17)30716-7/fulltext

antiHBVren

在HBeAg阳性慢性乙型肝炎患者中，使用ADV或ETV治疗，然后使用PEG-IFN alfa-2a治疗并不优于PEG-IFNα-2a单药治疗。
——干扰素的效果，与身体免疫激活情况的关系，还是不小；