96 weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection

被引：376

作者：

Agarwal, Kosh ^{[1
]}

Brunetto, Maurizia ^{[2
]}

Seto, Wai Kay ^{[3
]}

Lim, Young-Suk ^{[4
]}

Fung, Scott ^{[5
]}

Marcellin, Patrick ^{[6
]}

Ahn, Sang Hoon ^{[7
]}

Izumi, Namiki ^{[8
]}

Chuang, Wan-Long ^{[9
]}

Bae, Ho ^{[10
]}

Sharma, Manoj ^{[11
]}

Janssen, Harry L. A. ^{[12
,13
]}

Pan, Calvin Q. ^{[14
]}

Celen, Mustafa Kemal ^{[15
]}

Furusyo, Norihiro ^{[16
]}

Shalimar, Dr ^{[17
]}

Yoon, Ki Tae ^{[18
]}

Huy Trinh ^{[19
]}

Flaherty, John F. ^{[20
]}

Gaggar, Anuj ^{[20
]}

Lau, Audrey H. ^{[20
]}

Cathcart, Andrea L. ^{[20
]}

Lin, Lanjia ^{[20
]}

Bhardwaj, Neeru ^{[20
]}

Suri, Vithika ^{[20
]}

Subramanian, G. Mani ^{[20
]}

Gane, Edward J. ^{[21
]}

Buti, Maria ^{[22
]}

Chan, Henry L. Y. ^{[23
]}

机构：

[1] Kings Coll Hosp London, London, England

[2] Univ Pisa, Pisa, Italy

[3] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China

[4] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea

[5] Toronto Gen Hosp, Toronto, ON, Canada

[6] Hop Beaujon, Clichy, France

[7] Yonsei Univ, Seoul, South Korea

[8] Musashino Red Cross Hosp, Tokyo, Japan

[9] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan

[10] St Vincents Med Ctr, Asian Pacific Liver Ctr, Los Angeles, CA USA

[11] Inst Liver & Biliary Sci, New Delhi, India

[12] Toronto Western Hosp, Toronto, ON, Canada

[13] Erasmus MC, Rotterdam, Netherlands

[14] NYU, Sch Med, Langone Med Ctr, New York, NY USA

[15] Dicle Univ Hosp Infect Dis, Diyarbakir, Turkey

[16] Kyushu Univ Hosp, Fukuoka, Japan

[17] All India Inst Med Sci, Delhi, India

[18] Pusan Natl Univ, Yangsan Hosp, Yangsan, South Korea

[19] San Jose Gastroenterol, San Jose, CA USA

[20] Gilead Sci, Foster City, CA USA

[21] Auckland Clin Studies, Auckland, New Zealand

[22] Hosp Univ Valle Hebron, Barcelona, Spain

[23] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China

来源：

JOURNAL OF HEPATOLOGY | 2018年 / 68卷 / 04期

关键词：

Chronic hepatitis B virus; Bone safety; Renal safety; BONE-MINERAL DENSITY; NATURAL-HISTORY; DOUBLE-BLIND; ANTIVIRAL ACTIVITY; FANCONI SYNDROME; KIDNEY TOXICITY; SAFETY; DISEASE; EMTRICITABINE; MONOTHERAPY;

D O I：

10.1016/j.jhep.2017.11.039

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights

引用

页码：672 / 681

页数：10

共 34 条

[1] Twenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection [J].