AASLD2016[1844]改善肾实验室参数TAF比较TDF

StephenW

1844
Improved Renal Laboratory Parameters In CHB Patients
Treated With TAF Compared With Tenofovir Disoproxil
Fumarate (TDF)
Kosh Agarwal2, Norihiro Furusyo3, Kwan Soo Byun4, Jaeseok
Hwang5, John F. Flaherty1, Kyungpil Kim1, Anuj Gaggar1, Mani
Subramanian1, Maciej S. Jablkowski6, Alexey A. Yakovlev9, Huy
N. Trinh7, Maria Buti8; 1Gilead Sciences, Foster City CA, CA;
2Kings College Hospital NHS Trust, London, United Kingdom;
3Kyushu Medical Center, Fukuoka, Japan; 4Internal Medicine,
Korea University, Seoul, Korea (the Republic of); 5Keimyung University
Dongsan Medical Center, Daegu, Korea (the Republic of);
6Infectious and Liver Diseases, Oddziak Obserwacyjno-Zakazny,
Lodz, Poland; 7Silicon Valley Research Institute, San Jose, CA;
8Hospital Universitari Vall d’Hebron, Barcelona, Spain; 9Clinical
Infectious Diseases Hospital n.a. S.P.Botkin, St. Petersburg, Russian
Federation
Background: TDF treatment results in high rates of viral suppression
with no described resistance; however its use has
been associated with declines in eGFR over time. Phase 3
studies of TAF in CHB demonstrated lower declines in eGFR
compared to TDF over 48 weeks of treatment. Here, we further
characterize the clinical renal benefits of TAF compared to TDF.
Methods: In two identically-designed Phase 3 studies of TAF
(Study 110 in HBeAg positive and Study 108 in HBeAg negative
patients), patients were randomized 2:1 to TAF 25 mg QD
or TDF 300 mg QD, each with matching placebo, and treated
for 96 weeks. After Week 96, patients receive open label TAF
for 48 weeks. Renal parameters including eGFR calculated
by Cockcroft-Gault and CKD-EPI were evaluated throughout
the study period. Chronic kidney disease (CKD) staging was
categorized according to the NKF KDOQI guidelines (Stage
1: eGFR ≥ 90mL/min; Stage 2: eGFR 60-90 mL/min; Stage 3
eGFR 30-59 mL/min). Evaluated risk factors for kidney disease
included older age (age ≥ 50) and comorbidities of hypertension
(HTN), cardiovascular disease (CVD) and diabetes (DM).
Multivariate analysis was performed using backwards stepwise
approach. Results: Baseline demographics between TAF
and TDF groups in both studies were generally balanced for
risk factors for kidney disease. At week 48, patients treated
with TAF had smaller changes in creatinine (median change
0.01 mg/dL for TAF and 0.02 mg/dL for TDF; p=0.012) and
eGFRCG (median change -1.2 mL/min for TAF and -5.4 mL/min
for TDF; p<0.001) during 48 weeks of treatment. The number
of patients who had >25% eGFRCG reductions was also greater
in the TDF arm versus the TAF arm (14.5% vs 8.7%, p=0.002).
Using stages of CKD, a higher percentage of patients treated
with TDF had one or more stage worsening in renal function at
Week 48 (10.6% vs 6.7%; p=0.002; table). Among patients
at highest risk for kidney disease (older age and comorbidities
of HTN, CVD or DM), significantly more TDF-treated patients
had worsening of renal function compared to TAF-treated
patients. Multivariate analysis of worsening renal function by
CKD stage identified lower baseline eGFR, lower baseline
BMI, and Age ≥ 50 as independent predictors. Conclusions: In
patients with CHB, TAF therapy is associated with less effects
on renal parameters compared with TDF treatment. The benefits
of TAF may be particularly evident in patients at higher risk of
eGFR decline.
% Patients with Chronic Kidney Disease Stage Changes
HTN, hypertension; CVD, cardiovascular disease; DM, diabetes
Disclosures:
Kosh Agarwal - Advisory Committees or Review Panels: Gilead, BMS, Novartis,
Janssen, AbbVie; Consulting: MSD, Janssen, Achillion, Intercept; Grant/Research
Support: Roche, Gilead, BMS, Arbutus; Speaking and Teaching: Astellas, Gilead,
BMS, GSK
Kwan Soo Byun - Grant/Research Support: Gilead, BMS
John F. Flaherty - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Anuj Gaggar - Employment: Gilead Sciences, Inc.
Maciej S. Jablkowski - Advisory Committees or Review Panels: Gilead, Abbvie;
Consulting: BMS, Gilead, Roche, MSD; Speaking and Teaching: BMS, Roche,
MSD, Janssen-Cilag, Novartis
Huy N. Trinh - Grant/Research Support: Gilead, Intercept, Abbvie, merk; Speaking
and Teaching: Gilead; Stock Shareholder: Gilead
Maria Buti - Advisory Committees or Review Panels: Gilead, Janssen, MSD;
Grant/Research Support: Gilead, Janssen; Speaking and Teaching: Gilead,
Janssen, BMS
The following people have nothing to disclose: Norihiro Furusyo, Jaeseok
Hwang, Kyungpil Kim, Mani Subramanian, Alexey A. Yakovlev

StephenW

AASLD2016 [1844]改善肾实验室参数替诺福韦地索普比较
富马酸盐
改善肾实验室参数在CHB患者
与替诺福韦地索普比较
富马酸盐（TDF）
Kosh Agarwal2，Norihiro Furusyo3，Kwan Soo Byun4，Jaeseok
Hwang5，John F. Flaherty1，Kyungpil Kim1，Anuj Gaggar1，Mani
Subramanian1，Maciej S.Jablkowski6，Alexey A.Yakovlev9，Huy
N. Trinh7，Maria Buti8; 1Gilead Sciences，Foster City CA，CA;
2Kings College Hospital NHS Trust，伦敦，英国;
3 Kyushu Medical Center，Fukuoka，Japan; 4内科，
韩国大学，韩国首尔（共和国）; 5吉米大学
东山医疗中心，韩国（共和国）;
6传染病和肝病，Oddziak Obserwacyjno-Zakazny，
罗兹7硅谷研究所，加利福尼亚州圣何塞;
8Hospital Universitari Vall d'Hebron，Barcelona，Spain; 9临床
传染病医院S.P.Botkin，圣彼得堡，俄罗斯
联邦
背景：TDF治疗导致高的病毒抑制率
没有描述电阻;但是它的使用
与eGFR随时间的下降相关。阶段3
对CHB中TAF的研究表明eGFR降低较低
相比TDF超过48周的治疗。在这里，我们进一步
表征TAF与TDF相比的临床肾脏益处。
方法：在两个相同设计的3期TAF研究
（研究110在HBeAg阳性和研究108在HBeAg阴性
患者），将患者随机化为2：1至TAF 25mg QD
或TDF 300mg QD，每个与匹配的安慰剂，并治疗
持续96周。在第96周后，患者接受开放标签TAF
48周。肾脏参数包括eGFR计算
通过Cockcroft-Gault和CKD-EPI进行评价
研究期。慢性肾脏病（CKD）分期
根据NKF KDOQI指南分类（阶段
1：eGFR≥90mL/ min;阶段2：eGFR 60-90mL / min;阶段3
eGFR 30-59mL / min）。评估肾脏疾病的危险因素
包括年龄（年龄≥50岁）和高血压的合并症
（HTN），心血管疾病（CVD）和糖尿病（DM）。
使用向后逐步进行多变量分析
方法。结果：TAF之间的基线人口统计学
和TDF组在两项研究中总体上是平衡的
肾脏疾病的危险因素。在第48周，患者进行了治疗
与TAF有较小的肌酐变化（中值变化
TAF为0.01mg / dL，TDF为0.02mg / dL; p = 0.012）
eGFRCG（中值变化-1.2mL / min的TAF和-5.4mL / min
为TDF; p <0.001）。号码
的具有> 25％eGFRCG降低的患者也更大
在TDF组与TAF组相比（14.5％vs 8.7％，p = 0.002）。
使用CKD的阶段，治疗的患者百分比较高
与TDF有一个或多个阶段恶化的肾功能
第48周（10.6％对6.7％; p = 0.002;表）。患者中
在肾脏疾病的最高风险（年龄较大和合并症
的HTN，CVD或DM），显着更多的TDF治疗的患者
与TAF治疗相比肾功能恶化
耐心。恶性肾功能的多变量分析
CKD期确定较低的基线eGFR，较低的基线
BMI和年龄≥50作为独立预测因子。结论：
患者CHB，TAF治疗相关的影响较小
对肾脏参数与TDF治疗相比。好处
的TAF可能在更高风险的患者中特别明显
eGFR下降。
％慢性肾脏疾病阶段改变的患者
HTN，高血压; CVD，心血管疾病; DM，糖尿病
披露：
Kosh Agarwal - 咨询委员会或审查小组：G​​ilead，BMS，Novartis，
Janssen，AbbVie;咨询：MSD，杨森，Achillion，拦截;资助/研究
支持：罗氏，吉利德，BMS，杨梅;口语和教学：Astellas，Gilead，
BMS，GSK
Kwan Soo Byun - 资助/研究支持：Gilead，BMS
约翰·弗莱厄蒂 - 就业：吉利德科学;股票股东：Gilead Sciences
Anuj Gaggar - 就业：Gilead Sciences，Inc.
咨询委员会或审查小组：G​​ilead，Abbvie;
咨询：BMS，吉利德，罗氏，MSD;讲座和教学：BMS，Roche，
MSD，Janssen-Cilag，Novartis
Huy N. Trinh - 资助/研究支持：Gilead，Intercept，Abbvie，merk;请讲
和教学：Gilead;股票股东：Gilead
Maria Buti - 咨询委员会或审查小组：G​​ilead，Janssen，MSD;
资助/研究支持：Gilead，Janssen;口语和教学：Gilead，
Janssen，BMS
以下人士没有透露：Norihiro Furusyo，Jaesok
Hwang，Kyungpil Kim，Mani Subramanian，Alexey A. Yakovlev