96周治疗替诺福韦艾拉酚胺与替诺福韦二吡呋酯富马酸盐治疗

StephenW

96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection
Author links open overlay panelKoshAgarwal1MauriziaBrunetto2Wai KaySeto3Young-SukLim4ScottFung5PatrickMarcellin6Sang HoonAhn7NamikiIzumi8Wan–LongChuang9HoBae10ManojSharma11Harry L.A.Janssen1213Calvin Q.Pan14Mustafa KemalÇelen15NorihiroFurusyo16Dr.Shalimar17Ki TaeYoon18HuyTrinh19John F.Flaherty20AnujGaggar20Audrey H.Lau20Andrea L.Cathcart20LanjiaLin20NeeruBhardwaj20VithikaSuri20G.Mani Subramanian20Edward J.Gane21MariaButi22Henry L.Y.Chan23and the
GS-US-320-0110
Author links open overlay paneland
GS-US-320-0108 Investigators

1
    Kings College Hospital, London, United Kingdom

2
    University of Pisa, Pisa, Italy

3
    University of Hong Kong, Hong Kong

4
    Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

5
    Toronto General Hospital, Toronto, ON, Canada

6
    Hôpital Beaujon, Clichy, France

7
    Yonsei University, Seoul, South Korea

8
    Musashino Red Cross Hospital, Tokyo, Japan

9
    Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

10
    Asian Pacific Liver Center, St. Vincent Medical Center, Los Angeles, USA

11
    Institute of Liver and Biliary Sciences, New Delhi, India

12
    Toronto Western Hospital, Toronto, ON, Canada

13
    Erasmus Medical Center, Rotterdam, The Netherlands

14
    NYU Langone Medical Center, NYU School of Medicine, New York, USA

15
    Dicle University Hospital Infectious Diseases, Diyarbakir, Turkey

16
    Kyushu University Hospital, Fukuoka, Japan

17
    All India Institute of Medical Sciences, New Delhi, Delhi, India

18
    Pusan National University Yangsan Hospital, Yangsan, South Korea

19
    San Jose Gastroenterology, San Jose, USA

20
    Gilead Sciences, Foster City, CA, USA

21
    Auckland Clinical Studies, Auckland, New Zealand

22
    Hospital Universitario Valle Hebron, Barcelona, Spain

23
    The Chinese University of Hong Kong, Hong Kong

Received 3 August 2017, Revised 13 October 2017, Accepted 12 November 2017, Available online 17 January 2018.
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https://doi.org/10.1016/j.jhep.2017.11.039
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Highlights

•

    TAF is a new prodrug of tenofovir developed to treat patients with chronic HBV.
•

    A lower dose of TAF can be used because it delivers tenofovir more efficiently to hepatocytes than TDF.
•

    At week 48, TAF had non-inferior efficacy to TDF with improved renal and bone safety.
•

    Efficacy and safety results at week 96 confirm the 48-week results in both studies.

Background & Aims

Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection at a lower dose than tenofovir disoproxil fumarate (TDF) through more efficient delivery of tenofovir to hepatocytes. In 48-week results from two ongoing, double-blind, randomized phase III trials, TAF was non-inferior to TDF in efficacy with improved renal and bone safety. We report 96-week outcomes for both trials.
Methods

In two international trials, patients with chronic HBV infection were randomized 2:1 to receive 25 mg TAF or 300 mg TDF in a double-blinded fashion. One study enrolled HBeAg-positive patients and the other HBeAg-negative patients. We assessed efficacy in each study, and safety in the pooled population.
Results

At week 96, the differences in the rates of viral suppression were similar in HBeAg-positive patients receiving TAF and TDF (73% vs. 75%, respectively, adjusted difference −2.2% (95% CI −8.3 to 3.9%; p = 0.47), and in HBeAg-negative patients receiving TAF and TDF (90% vs. 91%, respectively, adjusted difference −0.6% (95% CI −7.0 to 5.8%; p = 0.84). In both studies the proportions of patients with alanine aminotransferase above the upper limit of normal at baseline, who had normal alanine aminotransferase at week 96 of treatment, were significantly higher in patients receiving TAF than in those receiving TDF. In the pooled safety population, patients receiving TAF had significantly smaller decreases in bone mineral density than those receiving TDF in the hip (mean % change −0.33% vs. −2.51%; p <0.001) and lumbar spine (mean % change −0.75% vs. −2.57%; p <0.001), as well as a significantly smaller median change in estimated glomerular filtration rate by Cockcroft-Gault method (−1.2 vs. −4.8 mg/dl; p <0.001).
Conclusion

In patients with HBV infection, TAF remained as effective as TDF, with continued improved renal and bone safety, two years after the initiation of treatment. Clinicaltrials.gov number: NCT01940471 and NCT01940341.
Lay summary

At week 96 of two ongoing studies comparing the efficacy and safety of tenofovir alafenamide (TAF) to tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B patients, TAF continues to be as effective as TDF with continued improved renal and bone safety.

Registration: Clinicaltrials.gov number: NCT01940471 and NCT01940

StephenW

96周治疗替诺福韦艾拉酚胺与替诺福韦二吡呋酯富马酸盐治疗乙型肝炎病毒感染
作者链接开放叠加panelKoshAgarwal1MauriziaBrunetto2Wai KaySeto3Young-SukLim4ScottFung5PatrickMarcellin6Sang HoonAhn7NamikiIzumi8Wan-LongChuang9HoBae10ManojSharma11Harry L.A.Janssen1213Calvin Q.Pan14MustafaKemalÇelen15NorihiroFurusyo16Dr.Shalimar17KiTaeYoon18HuyTrinh19John F.Flaherty20AnujGaggar20Audrey H.Lau20Andrea L.Cathcart20L​​anjiaLin20NeeruBhardwaj20VithikaSuri20G.Mani Subramanian20Edward J.Gane21MariaButi22Henry L.Y.Chan23and的
GS-US-320-0110
作者链接打开覆盖面板
GS-US-320-0108调查员

1
    国王学院医院，伦敦，英国

2
    比萨大学，意大利比萨

3
    香港大学，香港

4
    韩国首尔蔚山医科大学牙山医疗中心

五
    加拿大多伦多多伦多综合医院

6
    法国克利希的Beaujon医院

7
    韩国首尔延世大学

8
    日本东京武藏野红十字会医院

9
    高雄医科大学高雄医科大学附属医院高雄，台湾

10
    亚太肝脏中心，圣文森特医疗中心，美国洛杉矶

11
    印度新德里肝脏和胆道科学研究所

12
    多伦多西部医院，多伦多，ON，加拿大

13
    伊拉斯姆斯医疗中心，鹿特丹，荷兰

14
    美国纽约纽约大学医学院纽约大学Langone医学中心

15
    Dicle University Hospital Infectious Diseases，Diyarbakir，Turkey

16
    日本福冈九州大学医院

17
    全印度医学科学研究所，新德里，印度德里

18
    韩国梁山釜山国立大学梁山医院

19
    圣何塞胃肠病学，圣何塞，美国

20
    吉列德科学公司，美国加州福斯特市

21
    奥克兰临床研究，新西兰奥克兰

22
    Universitario Valle Hebron，西班牙巴塞罗纳

23
    香港中文大学，香港

2017年8月3日收到，2017年10月13日修订，2017年11月12日接受，2018年1月17日在线提供。
CROSSMARK车标
https://doi.org/10.1016/j.jhep.2017.11.039
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强调

•

    TAF是开发用于治疗慢性HBV患者的替诺福韦的新型前药。
•

    可以使用较低剂量的TAF，因为它比TDF更有效地将替诺福韦递送至肝细胞。
•

    在48周时，TAF对TDF具有非劣效性，肾和骨安全性得到改善。
•

    在第96周的功效和安全性结果证实了这两项研究中的48周结果。

背景和目的

替诺福韦艾拉酚胺（TAF）是替诺福韦的一种新型前药，用于治疗慢性乙型肝炎病毒（HBV）感染的患者，其剂量低于替诺福韦二吡呋酯富马酸盐（TDF），通过更有效地将替诺福韦递送至肝细胞。在两项正在进行的，双盲，随机III期临床试验的48周结果中，TAF的疗效并不劣于TDF，其肾功能和骨安全性均有所改善。我们报告这两项试验的96周结果。
方法

在两项国际试验中，慢性HBV感染患者以2：1的比例随机接受双盲方式接受25mg TAF或300mg TDF。一项研究招募了HBeAg阳性患者和其他HBeAg阴性患者。我们评估每项研究的疗效，以及汇总人群的安全性。
结果

在第96周时，接受TAF和TDF的HBeAg阳性患者的病毒抑制率差异相似（分别为73％和75％，调整后差异为-2.2％（95％CI为-8.3至3.9％; p = 0.47）;在接受TAF和TDF的HBeAg阴性患者中，分别为90％和91％，调整后的差异为-0.6％（95％CI为-7.0-5.8％，p = 0.84）丙氨酸转氨酶高于基线正常值上限，治疗96周时丙氨酸转氨酶水平正常的患者在接受TAF治疗的患者中显着高于接受TDF的患者，在合并安全性人群中，接受TAF治疗的患者骨密度高于接受TDF的患者（平均％变化-0.33％对-2.51％; p <0.001）和腰椎（平均％变化-0.75％对-2.57％; p <0.001）作为Cockcr估计的肾小球滤过率中值变化显着更小of-Gault法（-1.2比-4.8mg / dl; P <0.001）。
结论

在HBV感染的患者中，TAF保持与TDF一样有效，在开始治疗两年后，肾和骨安全性持续改善。 Clinicaltrials.gov编号：NCT01940471和NCT01940341。

antiHBVren

效果：
在第96周时，接受TAF和TDF的HBeAg阳性患者的病毒抑制率差异相似（分别为73％和75％，调整后差异为-2.2％（95％CI为-8.3至3.9％; p = 0.47）;
在接受TAF和TDF的HBeAg阴性患者中，分别为90％和91％，调整后的差异为-0.6％（95％CI为-7.0-5.8％，p = 0.84）丙氨酸转氨酶高于基线正常值上限，治疗96周时丙氨酸转氨酶水平正常的患者在接受TAF治疗的患者中显着高于接受TDF的患者，

副作用：
在合并安全性人群中，接受TAF治疗的患者骨密度高于接受TDF的患者（平均％变化-0.33％对-2.51％; p <0.001）和腰椎（平均％变化-0.75％对-2.57％; p <0.001）作为Cockcr估计的肾小球滤过率中值变化显着更小of-Gault法（-1.2比-4.8mg / dl; P <0.001）。

建议所有吃TDF的战友及时换TAF，少了副作用；
有个战友吃TDF肌酐低后，换TAF，吃了3个月还没有正常；