AASLD 2014: 替诺福韦酯单独或联合恩替卡韦在恩替卡韦

StephenW

231
Tenofovir Disoproxil Fumarate Alone or in Combination With Entecavir in Patients With Entecavir-Resistant Chronic Hepatitis B: Multicenter Randomized Trial
Young-Suk Lim1, Kwan Soo Byun2, Geum-Youn Gwak3, Byung
Chul Yoo3, So Young Kwon4, Yoon Jun Kim5, Jihyun An1, Han
Chu Lee1, Yung Sang Lee1;
1Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea;
2Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea;
3Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
4Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea;
5Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
Background/Aims:
It is not clear whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) combination therapy shows superior antiviral efficacy over tenofovir monotherapy in patients who harbor ETV-resistant hepatitis B virus (HBV).
Methods:
In this multicenter open-label trial, patients who had HBV with genotypic resistance mutations to ETV and serum HBV DNA concentration >60 IU/mL were randomized to TDF (300 mg/day) monotherapy (TDF group, n = 45) or to TDF and ETV (1 mg/day) combination therapy (TDF+ETV group, n = 45), and were included in the intention-to-treat analyses. Patients who had adefovir-resistant HBV (rtA181V/T and/or rtN236T) were excluded.
Results: At baseline, mean HBV DNA level was 4.28 +/- 1.60 log10 IU/mL. All 90 patients had at least one ETV-resistance mutations; rtT184 (n = 49), rtS202 (n = 43), or rtM250 (n = 7). All also had rtM204V/I +/- rtL180M mutations. One patient in the TDF group withdrew the consent at week 2. At week 48, the number of patients with HBV DNA <15 IU/mL, the primary efficacy endpoint, was 32 (71%) and 33 (73%) in the TDF and TDF+ETV groups, respectively (P=0.81). Mean reduction in HBV DNA levels from baseline was -3.65 +/- 1.64 log10 IU/mL and -3.77 +/- 1.30 log10 IU/mL in the TDF and TDF+ETV groups, respectively (P=0.69). Virological breakthrough was observed in a patient in the TDF group at 48 weeks, which was attributed to documented non-adherence to study drug. Only 7 and 5 patients in the TDF and TDF+ETV groups, respectively, had HBV DNA >60 IU/mL at 48 weeks, and were qualified for HBV resistance tests. Resistance mutations to lamivudine and/or ETV was detected only in 3 and 2 patients in the TDF and TDF+ETV groups, respectively, at 48 weeks. None developed additional resistance mutations. None in the TDF group required protocol-defined switch over of treatment. Both treatments were well tolerated, and safety and adverse event profiles were similar in the two groups.
Conclusions:
TDF monotherapy showed similarly high antiviral efficacy and safety as TDF and ETV combination therapy during 48 weeks of treatment in patients with ETV-resistant HBV. None developed additional resistance mutations.
KEY WORDS: Lamivudine, Monotherapy, Resistance, Virologic response

StephenW

231
富马酸替诺福韦酯单独或在患者与恩替卡韦耐药的慢性乙型肝炎联合恩替卡韦：多中心随机试验
英淑LIM1，关秀Byun2，今，妍Gwak3，秉
哲Yoo3，这么年轻Kwon4，尹君Kim5，Jihyun AN1，韩
楚Lee1，容生Lee1;
1Gastroenterology，峨山医学中心，医学，首尔，韩国的蔚山大学;
2Internal医学，医学，韩国首尔的韩国大学;
3Medicine，三星医疗中心，成均馆大学医学院，韩国汉城的;
4Internal医药，建国大学医学院，韩国汉城的;
5Internal医学，医学，韩国首尔的首尔国立大学
背景/目的：
目前尚不清楚富马酸替诺福韦酯（TDF）和恩替卡韦（ETV）联合疗法是否显示出优异的抗病毒效力超过诺福韦单药
谁在包庇恩替卡韦抗乙型肝炎病毒（HBV）的患者。
方法：
在这项多中心开放标签试验，谁曾与乙肝病毒基因型耐药突变恩替卡韦和血清HBV DNA浓度>60 IU/ mL的患者随机TDF（300毫克/天）单药治疗（TDF组，n=45）的患者，或TDF和恩替卡韦（1毫克/天）联合治疗（TDF+恩替卡韦组，n=45），并纳入意向性治疗分析。例谁阿德福韦耐药HBV（rtA181V/ T和/或的rtN236T）被排除在外。
结果：在基线水平，平均血清HBV DNA水平为4.28+/-1.60日志10国际单位/毫升。所有90名患者至少有一个ETV耐药突变; rtT184（N=49），rtS202（N
= 43），或rtM250组（n =7）。所有的也有rtM204V/ I+/- rtL180M突变。一名患者在TDF集团在退出时2星期同意48周，患者的HBV DNA<15 IU/ mL时，主要疗效终点，为32（71％）的数量
和33（73％）的TDF和TDF+恩替卡韦组，分别为（P =0.81）。平均降低HBV DNA水平从基线为-3.65+/-1.64日志10 IU/ mL和-3.77+/-1.30日志10国际单位/毫升的TDF和TDF+恩替卡韦组，分别为（P =0.69）。病毒学突破，观察在TDF组中的患者在48周，这是由于记录不遵守研究药物。在TDF和TDF+恩替卡韦组只有7和5例，分别有HBV DNA>60 IU/ mL的48周，并且是合格的乙肝病毒耐药检测。阻力
突变拉米夫定和/或恩替卡韦检测仅在3和2例在TDF和TDF+恩替卡韦组，分别为48周。未开发的附加电阻突变。概无TDF组中所需的协议定义的切换处理。两种治疗的耐受性良好，安全和
不良事件型材分别在两个组中相似。
结论：
TDF单药治疗过程中表现出治疗48周的患者，恩替卡韦耐药HBV同样高的抗病毒疗效和安全性为TDF与恩替卡韦联合用药。未开发的附加电阻突变。
关键词：拉米夫定单药治疗，耐药，病毒学应答