AASLD2014:（TDF）+干扰素α-2aHBsAg消失-全球随机对照试验结果

StephenW

193

HBsAg Loss with Tenofovir Disoproxil Fumarate (TDF) plus Peginterferon alfa-2a (PEG) in Chronic Hepatitis B (CHB): Results of a Global Randomized Controlled Trial
Patrick Marcellin1, Sang Hoon Ahn2, Xiaoli Ma3, Florin A. Caruntu4, Won Young Tak5, Magdy Elkashab6, Wan-Long Chuang7, Fehmi Tabak8, Rajiv Mehta9, Joerg Petersen10, Eduardo B. Martins11, Phillip Dinh11, Amoreena C. Corsa11, Prista Charuworn11, Mani Subramanian11, John G. McHutchison11, Maria Buti12, Giovanni B. Gaeta13, George V. Papatheodoridis14, Robert Flisiak15, Henry Lik-Yuen Chan16; 1Hopital Beaujon, University Paris-Diderot, Cli- chy, France; 2Division of Gastroenterology, Yonsei University Col- lege of Medicine, Seoul, Republic of Korea; 3Drexel University College of Medicine, Philadelphia, PA; 4National Institute for Infec- tious Diseases “ Matei Bals”, Bucharest, Romania; 5Kyungpook National University Hospital, Daegu, Republic of Korea; 6Toronto Liver Center, Toronto, ON, Canada; 7Kaohsiung Medical Univer- sity Chung-Ho Memorial Hospital, Kaohsiung City, Taiwan; 8Uni- versity of Istanbul, Istanbul, Turkey; 9Liver Clinic, Surat, India; 10IFI Institute for Interdisciplinary Medicine at the Asklepios Klinik St. George, University of Hamburg, Hamburg, Germany; 11Gilead Sciences, Foster City, CA; 12Hepatology Unit, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 13Viral Hepatitis Unit, Depart- ment of Infectious Diseases, Second University of Naples, Naples, Italy; 14Athens University Medical School, “Hippokration” General Hospital of Athens, Athens, Greece; 15Medical University of Bialystok, Poland; 16Department of Medicine and Therapeutics
and Institute of Digestive Disease, The Chinese University of Hong
Kong, Hong Kong SAR, Hong Kong

Background:
Rates of HBsAg loss in CHB patients treated with nucleos(t)ide analogues (NA) or PEG therapy are relatively low. Studies comparing PEG+NA combination therapy versus PEG alone are inconclusive. Here we present the Week 48 analysis of an ongoing trial evaluating TDF+PEG as combina- tion therapy. Methods: 740 patients with non-cirrhotic CHB were randomized 1:1:1:1 to receive TDF+PEG x48 weeks (Arm A); TDF+PEG x16 weeks followed by TDF x32 weeks (Arm B); continuous TDF (Arm C); PEG x48 weeks (Arm D). The primary hypotheses compared the rates of HBsAg loss, estimated by Kaplan-Meier method, at Week 72 for arms A vs C, A vs D, B vs C, and B vs D. The Week 48 analysis was pre-specified. Results: Of the 740 patients randomized and treated, 58.4% were HBeAg(+), mean age 37 years, 74.9% Asians and HBV genotype distribution (A, B, C, D, E-H) was 8.2%, 27.3%, 42.3%, 20.8% and 1.1%, respectively. At week 48, patients receiving PEG+TDF for 48 weeks had significantly higher rates of HBsAg loss than either TDF or PEG alone (fig- ure). Arm A had higher rates of HBs seroconversion (5.9%) than Arms B (0.6%), C (0%) or D (1.8%). Of the subjects with HBsAg loss, 73% were HBeAg(+) at baseline and had the following genotype distribution: 31.8% A, 36.4% B, 18.2% C, and 13.6% D. Rates of HBeAg loss were also higher in arms receiving PEG+TDF(Arm A 24.3%, Arm B 20.2%, Arm C 8.3%, Arm D 12.5%). HBV DNA suppression (HBV DNA < 15 IU/ml) was higher in the TDF-containing arms (Arm A 69.2%, Arm B 71.2%, Arm C 60.5%, Arm D 20.8%). No unexpected AEs were observed in the combination arms.
Conclusion: CHB patients treated with TDF and PEG combination therapy for 48 weeks achieved significantly higher rates of HBsAg loss than either therapy given alone.

StephenW

193
HBsAg消失了富马酸替诺福韦酯（TDF）加聚乙二醇干扰素α-2a干扰素（PEG）的慢性乙型肝炎（CHB）：全球随机对照试验结果
帕特里克Marcellin1，桑勋Ahn2，小莉MA3，弗罗林答Caruntu4，赢得年轻Tak5，Magdy Elkashab6，万龙Chuang7，Fehmi Tabak8，拉吉夫Mehta9，约尔格Petersen10，爱德华B. Martins11，菲利普Dinh11，Amoreena三Corsa11，普里斯塔Charuworn11，玛尼Subramanian11，约翰G. McHutchison11，玛丽亚Buti12，乔瓦尼二Gaeta13，乔治五世Papatheodoridis14，罗伯特Flisiak15，亨利力，玄Chan16; 1Hopital Beaujon，巴黎大学，狄德罗，CLI的CHY，法国; 2区消化内科，医学，韩国首尔的延世大学的同事根据法律; 3Drexel大学医学院，费城，宾夕法尼亚州; 4National研究所感染性疾病“马太巴尔斯”，布加勒斯特，罗马尼亚; 5Kyungpook国立大学医院，大邱，韩国; 6Toronto肝病中心，多伦多，加拿大; 7Kaohsiung医学中通用的sity仲和纪念医院，高雄市，台湾;伊斯坦布尔，伊斯坦布尔，土耳其8Uni-多样性; 9Liver诊所，苏拉特，印度; 10IFI研究所医学学科在阿斯科勒比俄斯KLINIK圣乔治，汉堡，德国汉堡大学; 11Gilead大学，加州福斯特城; 12Hepatology单位，医院Universitari瓦尔德希伯伦德，西班牙巴塞罗那; 13Viral肝炎组，传染病Depart-包换，那不勒斯，意大利那不勒斯第二大学; 14Athens大学医学院，雅典，雅典，希腊“Hippokration”综合医院;比亚韦斯托克，波兰15Medical大学;内科及药物治疗的16Department
和消化疾病，香港的中国大学研究所
香港，香港特区，香港

背景：
HBsAg消失慢性乙型肝炎患者的发生率与核苷（酸）类似物（NA）或PEG疗法治疗是比较低的。比较PEG + NA联合治疗对聚乙二醇单的研究仍未有定论。在这里，我们提出了48周的分析正在进行试验评估TDF+ PEG作为联合治疗的。方法：对740例非肝硬化慢性乙型肝炎患者随机1：1：1：1获得TDF+ PEG X48周（A组）; TDF+ PEG x16的周，然后TDF X32周（B组）;连续TDF（ARM C）; PEG X48周（杆d）。主要的假设比较HBsAg消失的速度，采用Kaplan-Meier法估计，在72周的手臂A对C，A与D，B与C和B与D的第48周的分析是预先指定的。结果：740例患者随机和治疗中，有58.4％为HBeAg（+），平均年龄37岁，74.9％的亚洲人和HBV基因型分布（A，B，C，D EH）为8.2％，27.3％，42.3％ ，20.8％和1.1％。 48周时，接受PEG+ TDF48周患者HBsAg消失比任何TDF或PEG单里（图）的显著率较高。 A组有HBs抗体血清转换（5.9％），比武器B（0.6％），C（0％）或D（1.8％）的比率较高。与HBsAg消失的受试者中，73％为HBeAg（+），在基线和具有下列基因型分布：31.8％A，36.4％B，18.2％C和13.6％D.价格HBeAg消失也高于接受武器PEG + TDF（A组24.3％，B组为20.2％，ARM C8.3％，杆d12.5％）。乙肝病毒DNA抑制（HBV DNA<15 IU/ ml）的是含有TDF武器高（A组69.2％，B组71.2％，ARM C60.5％，杆d20.8％）。没有意外的不良事件，观察相结合的武器。
结论：TDF和PEG组合治疗达到HBsAg消失的显著率高于单独给予任何治疗48周治疗慢性乙型肝炎患者。

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Conclusion: CHB patients treated with TDF and PEG combination therapy for 48 weeks achieved significantly higher rates of HBsAg loss than either therapy given alone.

咬牙硬挺

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肝肠欲断

TDF我国的还没上市，购买不方便又贵

shirlenna007

2012年我们打派的时候，身边不少人已经是挂床（办住院）打派罗欣了，也就是一针自费，带两针出来，大概一个月下来杂七杂八花费1500左右，替诺国内上市后，假如进医保前和博路定定价类似（因为在国外药店的恩替和替诺几乎同价，以此推算），大概一个月1000，这样加起来一个月2500。48周，11个月，差不多3万元整。如果看一整个疗程并不算很贵，对于大城市中等收入的家庭来说，我觉得值得一搏

shirlenna007

当然，如果替诺上市定价超出心理预期，和香港价格类似，那这个预算又要推高不少，所以，还是静观其变吧~~另外，我很早就听说会面市一种超长干扰素，一个月一针的，怎么没消息了？

MP4

肝肠欲断 发表于 2014-10-5 11:36
TDF我国的还没上市，购买不方便又贵

早已上市

MP4

shirlenna007 发表于 2014-10-5 23:35
当然，如果替诺上市定价超出心理预期，和香港价格类似，那这个预算又要推高不少，所以，还是静观其变吧~~另 ...

早已上市

shirlenna007

回复 MP4 的帖子

哦，抱歉我不在国内不太清楚，那请问是多少钱一瓶呢？我2012年买博路定的时候我们这个城市的是大约250一盒(7片），当时担心到国外没药吃还带了一堆过来现在都放在那儿等过期。。。