AASLD2019[476]切换后48周的安全性和有效性 从替诺福尔富马酸双

StephenW

476
SAFETY AND EFFICACY AT 48 WEEKS AFTER SWITCHING
FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO
TENOFOVIR ALAFENAMIDE (TAF) IN CHRONIC HBV PATIENTS
WITH RISK FACTORS FOR TDF USE
Maria Buti1, Pietro Lampertico2, Young-Suk LIM3, Kosh
Agarwal4, Scott K Fung5, Owen Tsang6, Magdy Elkhashab7,
Jia-Horng Kao8, Jose Luis Calleja9, Mandana Khalili10,
Natarajan Ravendhran11, Susanna Tan12, John F Flaherty12,
Anuj Gaggar12, Audrey H Lau12, George Wu12, Hie-Won
L. Hann13, Calvin Pan14, Hyung Joon Kim15, Patrick T F
Kennedy16 and Henry Lik Yuen Chan17, (1)Hospital General
Universitario Valle Hebron and Ciberehd, Barcelona, (2)
Gastroenterology and Hepatology, Fondazione Irccs Ca’
Granda O. Maggiore Policlinico, University of Milan, (3)
Department of Gastroenterology, Liver Center, Asan Medical
Center, University of Ulsan College of Medicine, (4)Institute
of Liver Studies, King’s College Hospital, (5)Toronto Centre
for Liver Disease, Toronto General Hospital, University Health
Network, (6)Princess Margaret Hospital, 2-10 Princess
Margaret Hospital Rd, Kwai Chung, Hong Kong, (7)Research,
Toronto Liver Centre, (8)Graduate Institute of Clinical
Medicine, National Taiwan University College of Medicine,
(9)Hospital Universitario Puerta De Hierro, (10)University of
California, San Fransisco, (11)Digestive Disease Associates,
PA, (12)Gilead Sciences, Inc, Foster City, California, USA,
(13)Thomas Jefferson University Hospital, Philadelphia, PA,
(14)Calvin Q. Pan Clinics, (15)Chung-Ang University College
of Medicine, (16)Barts Health NHS Trust, (17)The Chinese
University of Hong Kong, Hong Kong SAR
Background: TAF, a novel tenofovir prodrug, has
demonstrated noninferior efficacy to tenofovir disoproxil
fumarate (TDF) with a superior bone and renal safety profile
through 96 weeks in viremic CHB patients and through 48
weeks in virally suppressed patients who switched to TAF
from TDF TAF is a preferred treatment in the most recent
EASL and AASLD HBV Guidelines, especially in patients
with risk factors for TDF-associated renal and bone effects
We assessed safety and efficacy in virally suppressed CHB
patients with TDF risk factors (RF) who were switched from
TDF to TAF Methods: In a double-blind, active-controlled,
Phase 3 study, 488 CHB patients who were virologically
suppressed on TDF were randomized (1:1) to switch to TAF
or continue TDF for 48 weeks. Renal (serum creatinine [sCr],
eGFR by Cockcroft-Gault [eGFRCG] and urine biomarkers of
tubular function) and bone (serial DXA scans at hip/spine and
serum bone biomarkers) safety parameters, antiviral efficacy
(HBV DNA <20 IU/mL), and ALT normalization were assessed
in the subset of patients having baseline RF for TDF: Age >60
yr, osteoporosis of hip/spine, ≥Stage 2 chronic kidney disease
(CKD), albuminuria (UACR >30 mg/g), hypophosphatemia
(PO4 <2.5 mg/dL), or comorbidities associated with CKD (e.g.
HTN, DM, obesity) Results: Of 488 patients randomized and
treated, 358 (73%) had at least 1 RF, while 192 (39%) patients
had >2 RF present at baseline. Baseline demographics
of patients with at least 1 RF were similar between both
treatment groups: 30% with age >60 years , 66% male, 80%
Asian, 71% HBeAg-negative, median eGFRCG 84 mL/min, and
4% and 16% had osteoporosis at hip and spine, respectively
Renal and bone safety results at Week 48 are summarized
in the table. At Week 48, TDF patients switched to TAF
showed improvements in renal (sCr, eGFRCG) parameters
Improvements in hip and spine BMD were seen at 48 weeks
following switch. Antiviral efficacy was maintained in both
groups (HBV DNA <20 IU/mL: TAF 96.7% vs TDF 96.6%,
p=0 96) and TDF patients switching to TAF had similar rates
of normal ALT, and similar serological responses at Week 48.
Conclusion: CHB patients with risk factors for TDF toxicity
who are switched from TDF to TAF show improved bone and
renal safety parameters while efficacy was maintained at 48
weeks.

StephenW

476
切换后48周的安全性和有效性
从替诺福尔富马酸双异辛酯（TDF）到
慢性乙型肝炎患者中的替诺福尔阿拉法酰胺（TAF）
具有TDF使用风险因素
Maria Buti1，Pietro Lampertico2，Young-Suk LIM3，Kosh
Agarwal4，Scott K Fung5，Owen Tsang6，Magdy Elkhashab7，
Kao-Horng Kao8，Jose Luis Calleja9，Mandana Khalili10，
Natarajan Ravendhran11，Susanna Tan12，John F Flaherty12，
Anuj Gaggar12，Audrey H Lau12，George Wu12，Hie-Won
L.Hann13，Calvin Pan14，Hyung Joon Kim15，Patrick T F
肯尼迪16和李彦源17，（1）医院一般
巴塞罗那瓦莱希伯伦大学和西伯莱德大学，（2）
胃肠病学和肝病学，Fondazione Irccs Ca’
米兰大学的Granda O. Maggiore Policlinico，（3）
牙山医科大学肝病中心消化内科
蔚山医科大学中心，研究所（4）
国王学院医院肝脏研究学院，（5）多伦多中心
多伦多总医院肝病研究中心
网络（6）玛格丽特公主医院，2-10公主
香港葵涌玛格丽特医院路（7）研究部，
多伦多肝脏中心，（8）临床研究生院
国立台湾大学医学院医学系
（9）普埃塔·德耶罗大学医院，（10）
加利福尼亚州，旧金山，（11）消化系统疾病协会，
宾夕法尼亚州（12），Gilead Sciences，Inc，美国加利福尼亚州福斯特城，
（13）宾夕法尼亚州费城，托马斯·杰斐逊大学医院，
（14）卡尔文·潘诊所（15）中安大学学院
医学（16）巴茨健康NHS信托（17）
香港特别行政区香港大学
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）具有出色的骨骼和肾脏安全性
在病毒性CHB患者中持续96周，在48周中
接受TAF病毒抑制的患者接受治疗的几周时间
来自TDF的TAF是最近的首选治疗方法
EASL和AASLD HBV指南，尤其是患者
与TDF相关的肾脏和骨骼影响的危险因素
我们评估了病毒抑制的CHB的安全性和有效性
患有TDF危险因素（RF）的患者从
从TDF到TAF的方法：在双盲，主动控制，
3期研究中，有488名CHB患者接受了病毒学检查
将TDF抑制的患者随机（1：1）切换至TAF
或继续进行TDF 48周。肾（血清肌酐[sCr]，
Cockcroft-Gault的eGFR [eGFRCG]和尿液生物标志物
肾小管功能）和骨骼（在髋/脊柱和
血清骨生物标志物）安全参数，抗病毒功效
（HBV DNA <20 IU / mL）和ALT正常化
TDF基线RF的患者子集中：年龄> 60岁
年，髋/脊柱骨质疏松症，≥2期慢性肾脏疾病
（CKD），蛋白尿（UACR> 30 mg / g），低磷血症
（PO4 <2.5 mg / dL），或与CKD相关的合并症（例如
（HTN，DM，肥胖）结果：488例患者被随机分为
治疗的358（73％）患者至少有1次RF，而192（39％）患者
在基线处有> 2 RF。基线人口统计
至少有1个RF的患者之间相似
治疗组：30％年龄> 60岁，66％男性，80％
亚洲人，HBeAg阴性，占71％，eGFRCG中位数为84 mL / min，
髋部和脊柱骨质疏松症的患病率分别为4％和16％
总结了第48周的肾脏和骨骼安全性结果
在桌子上。在第48周，TDF患者改用TAF
显示肾参数（sCr，eGFRCG）有所改善
第48周，髋部和脊柱BMD有所改善
跟随开关。两者均保持抗病毒功效
组（HBV DNA <20 IU / mL：TAF 96.7％vs TDF 96.6％，
p = 0 96），而使用TAF的TDF患者发生率相似
正常ALT以及第48周的血清学反应相似。
结论：CHB患者有TDF毒性危险因素
从TDF转换为TAF的人的骨骼和
肾安全性参数，而疗效维持在48
周。