马来酸比索福韦酯与替诺福韦地索普西富马酸盐治疗慢性乙

StephenW

Clin Gastroenterol Hepatol. 2018 Nov 15. pii: S1542-3565(18)31244-8. doi: 10.1016/j.cgh.2018.11.001. [Epub ahead of print]
Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic HBV Infection.
Ahn SH1, Kim W2, Jung YK3, Yang JM4, Jang JY5, Kweon YO6, Cho YK7, Kim YJ8, Hong GY9, Kim DJ10, Um SH3, Sohn JH11, Lee JW12, Park SJ13, Lee BS14, Kim JH15, Kim HS16, Yoon SK17, Kim MY18, Yim HJ3, Lee KS1, Lim YS19, Lee WS20, Park NH21, Jin SY5, Kim KH22, Choi W23, Han KH24.
Author information

1
    Department of Internal Medicine, Yonsei 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, Korea University College of Medicine, Seoul, Korea.
4
    Department of Internal Medicine, Catholic University Medical College St. Vincent's Hospital, 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, Korea.
8
    Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
9
    Department of Internal Medicine, Kwangju 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, Pusan, 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.
21
    Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan, Korea.
22
    Department of Pharmacology, School of Medicine, Konkuk University, Korea.
23
    Ildong Pharmaceutical Co., Ltd., Seoul, Korea.
24
    Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. Electronic address: [email protected].

Abstract
BACKGROUND & AIMS:

Besifovir dipivoxil maleate (BSV) has activity against hepatitis B virus (HBV). We performed a phase 3 study to compare the antiviral efficacy and safety of BSV vs tenofovir disoproxil fumarate (TDF) in patients with chronic HBV infection in Korea.
METHODS:

We conducted a double-blind, non-inferiority trial of 197 patients with chronic HBV infection at 22 sites in South Korea, from November 2013 through February 2016. Patients were randomly assigned to groups given BSV (150 mg, n = 99) or TDF (300 mg, n = 98) for 48 weeks. We evaluated virologic responses to therapy (HBV DNA <69 IU/mL or 400 copies/ml), bone mineral density (BMD), and renal outcomes for safety analysis. The main efficacy endpoint was the proportion of patients with a virologic response at week 48. After 48 weeks, TDF was switched to BSV (150 mg) for an additional 48 weeks.
RESULTS:

After 48 weeks of treatment, 80.9% of patients given BSV and 84.9% of patients given TDF met the efficacy endpoint, indicating the non-inferiority of BSV to TDF. At week 96, 87.2% of patients in the BSV-BSV and 85.7% of patients in the TDF-BSV had a virologic response. At week 48, changes in hip and spine BMD differed significantly between the BSV and TDF groups, whereas the estimated glomerular filtration rate in the TDF group was significantly lower than that in the BSV group. However, at 96 weeks, there were no significant differences in BMD and estimated glomerular filtration rate between the BSV-BSV and TDF-BSV groups.
CONCLUSIONS:

BSV has antiviral efficacy comparable to that of TDF after 48 weeks of treatment, with durable effects for 96 weeks. BSV has a better safety profile than TDF, in terms of bone and renal outcomes. ClinicalTrials.gov no: NCT01937806.

Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS:

Antiviral therapy; Bone mineral density; Drug resistance; Hepatitis B; Nephrotoxicity; acyclic nucleotide phosphonate; drug resistance; eGFR; nephrotoxicity

PMID:
    30448598
DOI:
    10.1016/j.cgh.2018.11.001

StephenW

Clin Gastroenterol Hepatol。 2018年11月15日.pii：S1542-3565（18）31244-8。 doi：10.1016 / j.cgh.2018.11.001。 [提前打印]
马来酸比索福韦酯与替诺福韦地索普西富马酸盐治疗慢性乙型肝炎病毒感染的疗效和安全性。
Ahn SH1，Kim W2，Jung YK3，Yang JM4，Jang JY5，Kweon YO6，Cho YK7，Kim YJ8，Hong GY9，Kim DJ10，Um SH3，Sohn JH11，Lee JW12，Park SJ13，Lee BS14，Kim JH15，Kim HS16 ，Yoon SK17，Kim MY18，Yim HJ3，Lee KS1，Lim YS19，Lee WS20，Park NH21，Jin SY5，Kim KH22，Choi W23，Han KH24。
作者信息

1
    韩国延世大学医学院内科，韩国首尔。
2
    首尔国立大学医学院内科，首尔市政府Boramae医疗中心，韩国首尔。
3
    韩国首尔大学医学院内科。
4
    韩国水原市圣文森特医院天主教大学医学系内科。
五
    韩国首尔顺天乡大学医学院内科
6
    韩国大邱庆北国立大学医学院内科。
7
    韩国成均馆大学医学院Kangbuk三星医院内科
8
    首尔国立大学医学院内科和肝脏研究所，韩国首尔。
9
    韩国光州光州基督教医院内科
10
    韩国春川市哈利姆大学医学院内科。
11
    汉阳大学医学院内科，韩国首尔。
12
    韩国仁川仁荷大学医学院内科
13
    韩国釜山仁济大学白医院内科
14
    韩国大田忠南大学医学院消化内科和肝病学系。
15
    韩国仁川Gacheon大学医学院内科。
16
    韩国天安市顺天乡大学医学院内科
17
    韩国天主教大学内科，韩国首尔。
18
    延世大学内科，韩国原州原州医学院。
19
    韩国首尔蔚山大学医学院牙山医学系消化内科
20
    韩国光州全南大学医学院内科
21
    韩国蔚山蔚山大学内科学系。
22
    韩国建国大学医学院药理学系。
23
    Ildong Pharmaceutical Co.，Ltd.，Seoul，Korea。
24
    韩国延世大学医学院内科，韩国首尔。电子地址：[email protected]。

抽象
背景与目的：

Besifovir dipivoxil maleate（BSV）具有抗乙型肝炎病毒（HBV）的活性。我们进行了一项3期研究，以比较BSV与替诺福韦地索普西富马酸盐（TDF）在韩国慢性HBV感染患者中的抗病毒疗效和安全性。
方法：

我们对2013年11月至2016年2月期间在韩国22个地点的197名慢性HBV感染患者进行了一项双盲，非劣效性试验。患者被随机分配到给予BSV（150 mg，n = 99）或TDF的组中（300mg，n = 98），持续48周。我们评估了对治疗的病毒学应答（HBV DNA <69 IU / mL或400拷贝/ ml），骨矿物质密度（BMD）和肾脏结果进行安全性分析。主要疗效终点是在第48周时具有病毒学应答的患者的比例.48周后，将TDF转换为BSV（150mg）另外48周。
结果：

治疗48周后，80.9％给予BSV的患者和84.9％给予TDF的患者达到疗效终点，表明BSV对TDF的非劣效性。在第96周，BSV-BSV中87.2％的患者和TDF-BSV中85.7％的患者具有病毒学应答。在第48周，BSV组和TDF组之间髋部和脊柱BMD的变化显着不同，而TDF组中估计的肾小球滤过率显着低于BSV组。然而，在96周时，BSV-BSV和TDF-BSV组之间的BMD和估计的肾小球滤过率没有显着差异。
结论：

在治疗48周后，BSV具有与TDF相当的抗病毒效力，持续效果持续96周。就骨骼和肾脏结果而言，BSV具有比TDF更好的安全性。 ClinicalTrials.gov no：NCT01937806。

版权所有©2018 AGA Institute。由Elsevier Inc.出版。保留所有权利。
关键词：

抗病毒治疗;骨密度;耐药性;乙型肝炎;肾毒性;无环核苷酸膦酸酯;耐药性;表皮生长因子受体;肾毒性

结论：
    30448598
DOI:
    10.1016/j.cgh.2018.11.001