马来酸贝西福韦酯慢性乙型肝炎144周治疗：一项3期试验的开

StephenW

Am J Gastroenterol. 2020 May 1. doi: 10.14309/ajg.0000000000000605. [Epub ahead of print]
Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial.
Yim HJ1, Kim W2, Ahn SH3, Yang JM4, Jang JY5, Kweon YO6, Cho YK7, Kim YJ8, Hong GY9, Kim DJ10, Jung YK1, Um SH1, Sohn JH11, Lee JW12, Park SJ13, Lee BS14, Kim JH15, Kim HS16, Yoon SK17, Kim MY18, Lee KS3, Lim YS19, Lee WS20, Han KH3.
Author information

1
    Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
2
    Department of Internal Medicine, Seoul National University College of Medicine, Seoul Metropolitan Government Boramae Medical Center, Seoul, Korea.
3
    Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
4
    Department of Internal Medicine, Catholic University Medical College St. Vincent, Suwon, Korea.
5
    Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul, Korea.
6
    Department of Internal Medicine, Kyungpook National University College of Medicine, Daegu, Korea.
7
    Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
8
    Department of Internal Medicine, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
9
    Department of Internal Medicine, Gwangju Christian Hospital, Gwangju, Korea.
10
    Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea.
11
    Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
12
    Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea.
13
    Department of Internal Medicine, Paik Hospital, Inje University, Busan, Korea.
14
    Department of Gastroenterology and Hepatology, Chungnam National University School of Medicine, Daejeon, Korea.
15
    Department of Internal Medicine, Gacheon University College of Medicine, Incheon, Korea.
16
    Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
17
    Department of Internal Medicine, Catholic University of Korea, Seoul, Korea.
18
    Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.
19
    Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
20
    Department of Internal Medicine, Chonnam University Medical School, Gwangju, Korea.

Abstract
OBJECTIVES:

Chronic hepatitis B (CHB) remains a major worldwide public health concern. Besifovir dipivoxil maleate (BSV) is a new promising treatment for CHB. However, long-term efficacy and safety have not yet been evaluated. Therefore, the goal of the study is to determine the antiviral efficacy and safety of BSV treatment over a 144-week duration (BSV-BSV) in comparison with those of a sequential treatment with tenofovir disoproxil fumarate (TDF) followed by a 96-week duration BSV administration (TDF-BSV).
METHODS:

After 48 weeks of a double-blind comparison between BSV and TDF treatments, patients continued the open-label BSV study. We evaluated antiviral efficacy and drug safety up to 144 weeks for BSV-BSV and TDF-BSV groups. The primary endpoint was a virological response (hepatitis B virus DNA < 69 IU/mL).
RESULTS:

Among the 197 patients enrolled, 170 and 158 patients entered the second-year and third-year open-label phase extensional study, respectively, whereas 153 patients completed the 144-week follow-up. The virological response rate over the 144-week period was 87.7% and 92.1% in BSV-BSV and TDF-BSV groups, respectively (P = 0.36). The rates of ALT normalization and HBeAg seroconversion were similar between the groups. No drug-resistant mutations to BSV were noted. Bone mineral density and renal function were well preserved in the BSV-BSV group and were significantly improved after switching therapy in TDF-BSV patients.
DISCUSSION:

This extensional study of a phase 3 trial (NCT01937806) suggests that BSV treatment is efficacious and safe for long-term use in treatment-naïve and TDF-experienced patients with CHB.

PMID:
    32355123
DOI:
    10.14309/ajg.0000000000000605

StephenW

我是J胃肠。 2020年5月1日。doi：10.14309 / ajg.0000000000000605。 [Epub提前发行]
马来酸贝西福韦酯慢性乙型肝炎144周治疗：一项3期试验的开放标签扩展研究。
严HJ1，金W2，安SH3，杨JM4，张JY5，权YO6，赵YK7，金YJ8，洪GY9，金DJ10，郑YK1，Um SH1，孙JH11，李JW12，Park SJ13，李BS14，金JH15 ，Kim HS16，Yoon SK17，Kim MY18，Lee KS3，Lim YS19，Lee WS20，Han KH3。
作者信息

1个
高丽大学医学院内科，韩国首尔。
2
首尔市立大学医学院首尔市立大学Boramae医疗中心内科，韩国首尔。
3
延世大学医学院内科，韩国首尔。
4
韩国水原天主教大学圣文森特大学内科。
5
韩国首尔市淳春市大学医学院内科系。
6
韩国大邱庆北国立大学医学院内科。
7
成均馆大学医学院江北三星医院内科，韩国首尔。
8
首尔国立大学医学院肝脏研究所内科，韩国首尔。
9
韩国光州光州基督教医院内科。
10
韩国春川市哈林大学医学院内科。
11
汉阳大学医学院内科，韩国首尔。
12
韩国仁川大学医学研究所内科。
13
韩国釜山仁济大学白克医院内科。
14
韩国大田忠南国立大学医学院胃肠病学和肝病学系。
15
韩国仁川市佳川大学医学院内科。
16
淳春市大学医学院内科，韩国天安市。
17
韩国天主教大学内科，韩国首尔。
18岁
延世大学原州医学院内科，韩国原州市。
19
韩国蔚山大学医学院牙山医学中心消化内科。
20
韩国光州全南大学医学院内科。

抽象
目标：

慢性乙型肝炎（CHB）仍然是全球主要的公共卫生问题。马来酸倍西福韦酯（BSV）是CHB的一种新的有希望的治疗方法。但是，尚未评估长期疗效和安全性。因此，本研究的目的是确定与替诺福韦二富马酸富马酸盐（TDF）依次治疗96周后连续治疗（BSV-BSV）相比，在144周内BSV治疗的抗病毒疗效和安全性BSV持续时间管理（TDF-BSV）。
方法：

在对BSV和TDF治疗进行48周的双盲比较后，患者继续进行开放标签BSV研究。我们评估了BSV-BSV和TDF-BSV组长达144周的抗病毒效力和药物安全性。主要终点是病毒学应答（乙肝病毒DNA <69 IU / mL）。
结果：

在入组的197位患者中，分别有170位和158位患者进入了第二年和第三年开放标签期扩展研究，而153位患者完成了144周的随访。 BSV-BSV和TDF-BSV组在144周内的病毒学应答率分别为87.7％和92.1％（P = 0.36）。两组之间的ALT正常化和HBeAg血清转化率相似。没有发现对BSV有耐药性突变。在BSV-BSV组中，骨矿物质密度和肾功能得到了很好的保留，并且在TDF-BSV患者中进行切换治疗后，骨矿物质密度和肾功能得到了明显改善。
讨论：

这项对3期临床试验的扩展研究（NCT01937806）表明，对于未经治疗和TDF经验丰富的CHB患者，长期使用BSV是安全有效的。

PMID：
32355123
DOI：
10.14309 / ajg.0000000000000605