AASLD 2014:恩替卡韦和替诺福韦联合治疗慢性乙型肝炎

StephenW

230
The Safety and Efficacy of Entecavir and Tenofovir Combination Therapy for Chronic Hepatitis B in Patients with Previous Nucleos(t)ide Treatment Failure: Week 96 Results of the ENTEBE study
Fabien Zoulim1, Maciej S. Jablkowski2, Mircea. Diculescu3, Joerg
Petersen4, Patrick Marcellin5,6, Soumaya Bendahmane7, Aleksandra
Kedzierska8, Krzysztof. Simon9, Harry L. Janssen10,11;
1Hepatology Department, Hospices Civils de Lyon, INSERM U1052,
Lyon University, Lyon, France;
2Department of Infectious and Liver Diseases, Medical University of Lodz, Lodz, Poland;
3Centre of Gastroenterology and Hepatology, Fundeni Clinical Institute, Bucharest, Romania;
4IFI Institute for Interdisciplinary Medicine,Asklepios Klinik St Georg, Hamburg, Germany;
5Hôpital Beaujon, Assistance Publique Hôpitaux de Paris, University of Paris 7,
Paris, France;
6INSERM Unité 773, Centre de Recherches Claude Bernard sur les Hepatites Virales, Clichy, France;
7Bristol-Myers Squibb, Braine-I’Alleud, Belgium; 8Bristol-Myers Squibb, Rueil-Malmaison,France;
9Division of Infectious Diseases and Hepatology, Wroclaw University of Medicine, Wroclaw, Poland;
10Department of Gastroenterology & Hepatology, Erasmus Medical Center, university Medical Center Rotterdam, Rotterdam, Netherlands;
11Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada

Introduction:
In patients with chronic hepatitis B (CHB) who failed on prior nucleos(t)ide (NUC) therapy, rescue therapy should involve an effective antiviral regimen that is active against any existing drug-resistant hepatitis B virus (HBV) variants. Combination therapy with entecavir (ETV) and tenofovir disoproxil fumarate (TDF), two potent agents with non-overlapping resistance profiles, may provide a single regimen suitable for all patients who failed on other NUC regimens. Here we present Week 96 results of the ENTEBE study assessing ETV+TDF for patients with prior failure on NUC therapy.
Methods:
In this single-arm, open-label, multicenter study, CHB patients with prior non-response, partial response, or virologic breakthrough on NUC therapy were treated with ETV (1 mg) plus TDF (300 mg) for 96 weeks. The primary endpoint was the proportion of patients with HBV DNA <50 IU/mL (Roche COBAS TaqMan-HPS Assay) at Week 48 (non-completer=-failure). Secondary endpoints included proportions of patients with antiviral responses at Week 96, safety, and resistance to ETV or adefovir (ADV).
Results: Overall, 92 patients were treated; 6 patients discontinued prior to Week 96. At baseline, 65% of patients were HBeAg(+), median HBV DNA was 3.7 log10 IU/mL. Prior NUC treatment included monotherapy with ETV (53%), lamivudine (LVD; 22%), TDF (12%), (ADV; 4%), or telbivudine (LdT; 2%), or combinations of these agents (7%); 58% of patients had evidence of single- or multidrug resistance mutations (LVD: 52%, ETV: 26%; ADV: 7%). At Week 48, 76% (70/92) of patients achieved the primary endpoint (HBV DNA <50 IU/mL). By Week 96, 85% (78/92) of patients had HBV DNA <50 IU/mL, including 80% (16/20) with prior failure on LVD, 100% (4/4) on ADV, 88% (42/48) on ETV, 82% (9/11) on TDF, 100% (2/2) on LdT, and 83% (5/6) on combination therapy. No treatment-emergent resistance to ETV or ADV was observed. Six patients had on-treatment serious adverse events, none of which were considered related to study treatment. One patient died from hepatocellular carcinoma.
Conclusions: In patients who failed prior NUC therapy, 96 weeks of ETV+TDF
combination therapy was well tolerated and achieved virologic suppression in the majority (85%) of patients, irrespective of the type of prior NUC, with no new resistance development.

StephenW

230
安全和恩替卡韦和替诺福韦联合治疗慢性乙型肝炎的疗效在患者既往核苷（酸）IDE治疗失败：本周的ENTEBE研究结果96
法比安斯基Zoulim1，马切伊南Jablkowski2，米尔恰。 Diculescu3，约尔格
Petersen4，帕特里克Marcellin5,6，Soumaya Bendahmane7，亚历山德拉
Kedzierska8，克日什托夫。 Simon9，哈利属Janssen10,11;
1Hepatology处，收容所Civils里昂，INSERM U1052，
里昂大学，法国里昂;
教研室的传染病和肝病，罗兹，波兰罗兹医科大学;
3Centre胃肠病学和肝病，Fundeni临床研究所，布加勒斯特，罗马尼亚;
4IFI研究所跨学科医学，阿斯科勒比俄斯KLINIK圣乔治，汉堡，德国;
5HôpitalBeaujon，协助Publique医院临床巴黎，巴黎7大学
法国巴黎;
6INSERM团结773，中心德Recherches克劳德·伯纳德河畔莱Hepatites Virales，克利希，法国;
7Bristol-Myers Squibb公司，布雷恩 -  I'Alleud，比利时; 8Bristol-Myers Squibb公司，吕埃马迈松，法国;
9Division传染病和肝病，医药，弗罗茨瓦夫，波兰的弗罗茨瓦夫大学;
10Department肠胃肝脏，伊拉斯谟医疗中心，大学医疗中心鹿特丹，鹿特丹，荷兰;
11Liver诊所，多伦多西部及综合医院，大学健康网络，多伦多，加拿大

简介：
慢性乙型肝炎（CHB）谁没有事先核苷（酸）IDE（NUC）治疗，抢救治疗应该包括有效抗病毒治疗方案是积极的
针对任何现有的耐药乙型肝炎病毒（HBV）的变体。组合疗法恩替卡韦（ETV）和富马酸替诺福韦酯（TDF），两个强效剂与非重叠电阻剖面，可以提供一个单一疗法
适合谁没有在其他国统疗法的患者。在这里，我们提出了96周的结果ENTEBE研究评估教育电视+ TDF患者对国统疗法之前失败的。
方法：
在此单臂，开放标签，多中心研究，慢性乙型肝炎患者与现有的非响应，部分响应，或病毒学突破上NUC治疗患者采用ETV（1毫克）加TDF（300毫克）进行96周。主要终点是患者的HBV DNA<50 IU/毫升（罗氏COBAS TaqMan探针-HPS法）第48周（非补足=-failure）的比例。次要终点包括患者的抗病毒反应的比例为96周，安全性和耐恩替卡韦或阿德福韦（ADV）。
结果：总体而言，92例患者进行治疗; 6例前周96在基线停产，65％的患者为HBeAg（+），HBV DNA中位数为3.7
日志10国际单位/毫升。现有NUC治疗包括单用ETV（53％），拉米夫定（LVD;22％），TDF（12％），（ADV，4％），或替比夫定（LDT2％），或这些试剂的组合，（7％ ）; 58％的患者有单或耐药突变（LVD：52％，ETV为26％，ADV：7％）的证据。在第48周时，76％的患者（九十二分之七十○）取得的主要终点（HBV DNA<50 IU / mL）中。经96周，85％的患者（九十二分之七十八）的HBV对阿德福韦的DNA<50 IU/ mL时，其中80％（16/20）与LVD先前失败，100％（4月4日），88％（42 / 48）上ETV，在TDF上LDT82％（911事件），100％（2/2），和83％（5或6）上的联合治疗。否ETV或ADV治疗出现耐药观察。六名病人对治疗的严重不良事件，其中没有一个被认为与研究治疗。一名患者从肝癌去世。
结论：谁没有事先NUC治疗的患者，96周恩替卡韦+ TDF的
联合治疗耐受良好，并在患者中，大部分（85％）达到病毒学抑制，而不论之前NUC的类型的，没有新的抗性发展。

肝肠欲断

辛苦了

tonychant

价格谁能承受？

hp121

效果是好
但是杀鸡用牛刀吧？？

再说药物多了始终副作用大
除非耐药了
否则单独一种也就够了

价格嘛，最便宜渠道，一年应该不到1万吧