AASLD2019[483]替诺福韦治疗的有效性和安全性 病毒性慢性抑制

StephenW

483
EFFICACY AND SAFETY OF SWITCHING TO TENOFOVIR
ALAFENAMIDE (TAF) IN VIRALLY SUPPRESSED CHRONIC
HEPATITIS B (CHB) PATIENTS WITH RENAL IMPAIRMENT:
WEEK 24 RESULTS FROM A PHASE 2 OPEN-LABEL STUDY
Harry L. A. Janssen1, Young-Suk LIM2, Edward J. Gane3,
Claire Fournier4, Sang Hoon Ahn5, Owen Tsang6, Wan Long
Chuang7, Jeong Heo8, Aric Josun Hui9, Magdy Elkhashab10,
Chi-Yi Chen11, Wei-Wen Su12, John F Flaherty13, Anuj
Gaggar14, Susanna Tan15, Audrey H Lau16, Vithika Suri16,
Shuyuan Mo16, Mani Subramanian13, Syed-Mohammed Jafri17,
Kosh Agarwal18, Pietro Lampertico19, Giulo Marchesini20,
Carla S. Coffin21 and Yi-Hsiang Huang22, (1)Toronto Centre
for Liver Disease, Toronto General Hospital, University
Health Network, (2)Gastroenterology, Asan Medical Center,
University of Ulsan College of Medicine, Seoul, Republic of
Korea, (3)Auckland Clinical Studies, Auckland, New Zealand,
(4)CHUM, Service D’hépatologie, Montreal, Canada, (5)
Yonsei Liver Center, Severance Hospital, (6)Princess
Margaret Hospital, 2-10 Princess Margaret Hospital Rd,
Kwai Chung, Hong Kong, (7)Kaohsiung Medical University
Hospital, Kaohsiung, Taiwan, (8)Medical Research Institute,
Pusan National University Hospital, Busan, Korea, (9)Alice
Ho Miu Ling Nethersole Hospital, (10)Research, Toronto
Liver Centre, (11)Department of Internal Medicine, Chia-Yi
Christian Hospital, Chia-Yi, Taiwan, (12)Changhua Christian
Hospital, Changhua, Taiwan, (13)Gilead Sciences, Inc., (14)
Gilead Sciences Inc., Foster City, CA, (15)Gilead Sciences,
Inc, Foster City, California, USA,, (16)Gilead Sciences, Inc,
Foster City, California, USA, (17)Gastroenterology, Henry
Ford Hospital, (18)Institute of Liver Studies, King’s College
Hospital, (19)Gastroenterology and Hepatology, Fondazione
Irccs Ca’ Granda O. Maggiore Policlinico, University of
Milan, (20)University of Bologna, (21)Medicine, University of
Calgary, (22)Division of Gastroenterology and Hepatology,
Department of Medicine, Taipei Veterans General Hospital
Background: TAF, a novel tenofovir prodrug, has
demonstrated noninferior efficacy to tenofovir disoproxil
fumurate (TDF) with superior bone and renal safety in virally
suppressed CHB patients with eGFR (by Cockcroft-Gault;
eGFRCG) ≥50 mL/min when switched from TDF. Efficacy
and safety of virally suppressed patients on TDF with renal
impairment who were switched to TAF were evaluated in this
Phase 2 study Methods: CHB patients with renal impairment
receiving TDF for ≥48 weeks and virally suppressed for ≥6
months with HBV DNA <20 IU/mL at screening were enrolled
into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG
15 to <60mL/min) and 2) end stage renal disease (ESRD)
(eGFRCG <15 mL/min) on chronic hemodialysis (HD) All
patients were switched to TAF 25 mg once daily for 96 weeks
Co-primary endpoints were proportion with HBV DNA <20 IU/
mL and graded adverse events (AEs)/lab abnormalities at
Week 24. Key secondary safety endpoints were changes in
hip and spine bone mineral density (BMD) and serum markers
of bone turnover (Table), as well as changes in eGFRCG
and urinary markers of tubular function (mod-severe renal
impairment group only) Results: 93 patients (moderatesevere
impairment 78; ESRD 15) were enrolled from 26 sites
in 8 countries Median age was 65 years, 74% male, 77%
Asian, 83% HBeAg-negative, up to 60% had low BMD at hip
and/or spine, and 60% and 24% had a history of hypertension
and/or diabetes mellitus, respectively. Key efficacy/safety
results at Week 24 are summarized in the Table. All patients
on treatment at Week 24 maintained HBV DNA <20 IU/mL and
a high proportion had normal ALT levels Relative to baseline
levels, switching to TAF from TDF resulted in increases in
hip and spine BMD, decreases in bone turnover markers,
as well as an increase in eGFRCG and improved markers of
renal tubular function TAF was well tolerated with few having
Grade 3 or 4 AEs (7 5%); no serious AEs related to study drug
and no discontinuations due to AEs Conclusion: In renallyimpaired
CHB patients, including ESRD patients on HD, viral
suppression was well maintained and the bone and renal
safety were improved 24 weeks after switching from TDF to
TAF.

StephenW

483
替诺福韦治疗的有效性和安全性
病毒性慢性抑制的阿糖胺（TAF）
患有肾功能不全的乙型肝炎（CHB）患者：
第2阶段开放式研究的第24周结果
哈里·扬·詹森（Harry L. A.
克莱尔·弗尼尔（Claire Fournier）4，桑勋安（Sang Hoon Ahn）5，曾荫权（Owen Tsang）6，万隆（Wan Long）
庄7，郑赫8，艾力·许孙辉9，麦迪·艾尔卡沙布10，
陈志义11，苏维文12，约翰·弗莱厄蒂13，阿努吉
Gaggar14，Susanna Tan15，Audrey H Lau16，Vithika Suri16，
淑媛Mo16，玛尼Subramanian13，赛义德-穆罕默德Jafri17，
Kosh Agarwal18，Pietro Lampertico19，Giulo Marchesini20，
卡拉·S·科芬（Carla S.Coffin）21和黄以祥（22），（1）多伦多中心
大学多伦多总医院肝病科
卫生网络（2）牙山医学中心消化内科
蔚山大学医学院，首尔
韩国（3）奥克兰临床研究中心，新西兰奥克兰，
（4）CHUM，服务D'hépatologie，加拿大蒙特利尔，（5）
遣散医院延世肝病中心（6）公主
玛格丽特公主医院路2-10号玛格丽特医院
香港葵涌（7）高雄医科大学
台湾高雄医院，（8）医学研究所，
韩国釜山釜山国立大学医院（9）爱丽丝
何妙龄那打素医院（10）研究，多伦多
嘉义市肝病中心（11）内科
台湾嘉义基督教医院，（12）彰化基督教
台湾彰化医院（13）吉利德科学公司（14）
加利福尼亚州福斯特市的吉利德科学公司（15）
Inc，美国加利福尼亚州福斯特市，（16）Gilead Sciences，Inc，
美国加利福尼亚州福斯特城，（17）亨利肠胃病学
福特医院（18）国王学院肝病研究所
医院（19）胃肠病学和肝病学
爱尔兰大学的Irccs Ca’Granda O. Maggiore Policlinico
米兰，（20）博洛尼亚大学，（21）医学，
卡尔加里（22）胃肠病和肝病科，
台北荣民总医院内科
背景：TAF是一种新型替诺福韦前药，具有
证明对替诺福韦二甲酚非劣效
富马酸盐（TDF）在病毒方面具有优异的骨骼和肾脏安全性
抑制CHB的eGFR患者（Cockcroft-Gault；
从TDF切换到eGFRCG）≥50 mL / min。功效
TDF合并肾脏的病毒抑制患者的安全性和安全性
在此评估了转为TAF的障碍
2期研究方法：CHB肾功能不全的患者
接受TDF≥48周并被病毒抑制≥6
筛选时的HBV DNA <20 IU / mL数月
分为2组：1）中重度肾功能不全（eGFRCG
15至<60mL / min）和2）晚期肾病（ESRD）
（eGFRCG <15 mL / min）进行慢性血液透析（HD）全部
患者每周一次转用TAF 25 mg治疗96周
共同主要终点指标与HBV DNA <20 IU /
mL和分级不良事件（AEs）/实验室异常
第24周。主要的次要安全性指标是
髋和脊柱骨矿物质密度（BMD）和血清标志物
骨周转率（表）以及eGFRCG的变化
和肾小管功能指标（重度肾功能不全）
结果：93例（中度—重度）
减值78; ESRD 15）来自26个站点
在8个国家/地区中位数年龄为65岁，男性74％，77％
亚洲人，83％的HBeAg阴性，高达60％的髋关节BMD低
和/或脊柱，分别有60％和24％有高血压病史
和/或糖尿病。关键功效/安全性
表中总结了第24周的结果。所有病人
在第24周接受治疗时，HBV DNA维持<20 IU / mL，
相对于基线，高比例的ALT水平正常
级别，从TDF切换到TAF导致
髋部和脊柱BMD，骨转换标志物减少，
以及eGFRCG的增加和改善的标记
肾小管功能性TAF耐受性良好，很少
3或4级AE（7 5％）;没有与研究药物相关的严重不良事件
且未因AE停药结论：肾功能不全
CHB患者，包括高清，病毒性ESRD患者
抑制良好，骨骼和肾脏
从TDF切换到TDF后24周，安全性得到改善
TAF。