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J Hepatol. 2018 Apr;68(4):672-681. doi: 10.1016/j.jhep.2017.11.039. Epub 2018 Jan 17.

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

Author information

1
Kings College Hospital, London, United Kingdom. Electronic address: kosh.agarwal@nhs.net.
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; Erasmus Medical Center, Rotterdam, The Netherlands.
13
NYU Langone Medical Center, NYU School of Medicine, New York, USA.
14
Dicle University Hospital Infectious Diseases, Diyarbakir, Turkey.
15
Kyushu University Hospital, Fukuoka, Japan.
16
All India Institute of Medical Sciences, New Delhi, Delhi, India.
17
Pusan National University Yangsan Hospital, Yangsan, South Korea.
18
San Jose Gastroenterology, San Jose, USA.
19
Gilead Sciences, Foster City, CA, USA.
20
Auckland Clinical Studies, Auckland, New Zealand.
21
Hospital Universitario Valle Hebron, Barcelona, Spain.
22
The Chinese University of Hong Kong, Hong Kong. Electronic address: hlychan@cuhk.edu.hk.

Abstract

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 NCT01940341.

KEYWORDS:

Bone safety; Chronic hepatitis B virus; Renal safety

PMID:
29756595
DOI:
10.1016/j.jhep.2017.11.039

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