AASLD2014:Tenofovir (TDF)两个第3期试验8年结果

StephenW

Long Term Treatment with Tenofovir Disoproxil Fuma- rate for Chronic Hepatitis B Infection is Safe and Well Tolerated and Associated with Durable Virologic Response with no Detectable Resistance: 8 Year Results from Two Phase 3 Trials
Patrick Marcellin1, Edward J. Gane2, Robert Flisiak3, Huy N. Trinh4, Joerg Petersen5, Selim Gurel6, Kelly D. Kaita7, Iskren A. Kotzev8, Naoky Tsai9, John F. Flaherty10, Raul E. Aguilar Schall10, Kathryn M. Kitrinos10, Mani Subramanian10, John G. McHutchi- son10, Jacob George11, Harry L. Janssen12, Maria Buti13; 1Hopital Beaujon, Clichy, France; 2Auckland City Hospital, Auckland, New Zealand; 3Medical University of Bialystok, Bialystok, Poland; 4San Jose Gastroenterology, San Jose, CA; 5Asklepiosklinik St. Georg, University of Hamburg, Hamburg, Germany; 6Uludag Universitesi Tip Fakultesi, Bursa, Turkey; 7University of Manitoba, Winnipeg, MB, Canada; 8University Hospital Sveta Marina, Varna, Bulgaria; 9Queens Medical Center, University of Hawaii, Honolulu, HI; 10Gilead Sciences, Foster City, CA; 11Storr Liver Unit, Westmead Millennium Institute, Westmead Hospital, Sydney, NSW, Australia; 12University of Toronto, Toronto, ON, Canada; 13Universitari Vall d’Hebron and Ciberehd, Barcelona, Spain
Background: Through 5 years of treatment with tenofovir diso- proxil fumarate (TDF) in mostly naïve patients, we reported sustained viral suppression with regression of fibrosis, and reversal of cirrhosis in 74% of patients (Lancet 2013;381:468- 75). Further, no evidence of resistance to TDF was seen through Year 6 (J Hepatol. 2014;59:434-42). Here we present Year 8 results, the initially pre-specified end of study period, for two Phase 3 studies in HBeAg- and HBeAg+ chronic hepatitis B patients. Methods: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, all patients were eligible to con- tinue open-label TDF. Patients were assessed every 3 months for efficacy and safety; resistance surveillance was performed annually, and annual bone mineral density (BMD) assessments by DXA were included starting at Year 4. Results: A total of 641 patients were randomized and treated; 585 (91%) entered the TDF extension phase at Year 1, and 412 (64%) remained on study at Year 8. Efficacy results are summarized in the table. Durable viral suppression was maintained, and 7 additional patients (5 HBeAg+ and 2 HBeAg- ) experienced loss of HBsAg (5 patients with seroconversion to anti-HBs) between Years 5-8. No resistance to TDF was detected through Year 8. Through Year 8, a confirmed renal event (either ≥0.5 mg/dL increase in serum creatinine, or serum phosphorus <2 mg/dL, or creatinine clearance <50 mL/min) was observed in 2.2% of patients, and BMD (T scores) of hip and spine were stable between Years 4-8.
Tags: tenofovir, aasld

StephenW

用替诺福韦Fuma-率在慢性乙型肝炎病毒感染长期治疗是安全的，耐受性良好，并伴有持久病毒学应答没有检测到
耐药：从两个第3期试验8年结果
帕特里克Marcellin1，爱德华·J·Gane2，罗伯特Flisiak3，伊北Trinh4，约尔格Petersen5，塞利姆Gurel6，凯利D. Kaita7，Iskren答Kotzev8，Naoky Tsai9，约翰·Flaherty10，劳尔大肠杆菌阿吉拉尔Schall10，凯瑟琳M. Kitrinos10 ，玛尼Subramanian10，约翰G. McHutchi- SON10，雅各George11，哈里L。Janssen12，玛丽亚Buti13; 1Hopital Beaujon，克利希，法国; 2Auckland市医院，奥克兰，新西兰;比亚韦斯托克，比亚韦斯托克，波兰3Medical大学; 4San何塞消化内科，圣何塞，加利福尼亚; 5Asklepiosklinik圣乔治，汉堡，德国汉堡大学; 6Uludag Universitesi提示Fakultesi，布尔萨，土耳其; 7University马尼托巴省，温尼伯，马尼托巴省，加拿大; 8University医院斯韦塔卡特码头，保加利亚瓦尔纳; 9Queens医疗中心，夏威夷，檀香山，夏威夷大学; 10Gilead大学，加州福斯特城; 11Storr肝单位，威斯特米德千年研究所，韦斯特米德医院，悉尼，新南威尔士，澳大利亚; 12University多伦多，多伦多，加拿大; 13Universitari瓦尔德希伯伦和Ciberehd，巴塞罗那，西班牙
背景：经过5年多为初治患者使用替诺福韦diso- proxil富马酸（TDF）治疗，我们报道了持续的病毒抑制肝硬化与肝纤维化的回归，以及逆转的患者74％（柳叶刀2013，381：468-75） 。此外，没有证据表明抗TDF，通过6年被看见（。肝脏病学杂志2014;59：434-42）。在这里，我们提出了8年的结果，研究周期的开始预先指定年底，第二阶段3研究在个HBeAg-和HBeAg阳性慢性乙型肝炎患者。方法：48周TDF的阿德福韦酯双盲对比后，所有患者均符合以继续开放标签TDF。患者进行评估，每3个月的疗效和安全性;在每年进行耐药性监测，并每年骨矿物质密度（BMD）由DXA评估纳入起始年4结果：共有641例患者随机和治疗; 585（91％）进入TDF延伸相位在第1年，和412（64％）残留在研究在年8功效结果总结在表中。持久抑制病毒，保持和增加7个病人（5 HBeAg阳性和2个HBeAg-）出现亏损的HBsAg（5例血清学转换为抗HBs）5-8年之间。到TDF无阻力通过年8检测到的透年8所示，证实肾事件（或者≥0.5mg / dL的增加，血清肌酐，或血清磷<2毫克/升，或肌酸酐清除率<50毫升/分钟），观察患者髋部和脊柱的2.2％，与骨密度（T值）4-8年间保持稳定。
标签：替诺福韦，AASLD

齐欢畅2

好文，再次证明替诺福伟是很好的药物。中国已经仿制，看来能够造福人群。赞楼主。

wsl105

咬牙硬挺

非常高兴，希望一辈子不耐药

MP4

齐欢畅2 发表于 2014-10-3 21:21
好文，再次证明替诺福伟是很好的药物。中国已经仿制，看来能够造福人群。赞楼主。 ...

中国已经上市，目前没仿制药