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Clinical Trial
. 2021 Dec 20;21(1):489.
doi: 10.1186/s12876-021-02008-9.

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study

Fumitaka Suzuki  1 , Yoshiyuki Suzuki  2 , Yoshiyasu Karino  3   4 , Yasuhito Tanaka  5   6 , Masayuki Kurosaki  7 , Hiroshi Yatsuhashi  8 , Tomofumi Atarashi  9 , Masanori Atsukawa  10 , Tsunamasa Watanabe  11 , Masaru Enomoto  12 , Masatoshi Kudo  13 , Naoto Maeda  14 , Hiroshi Kohno  15 , Kouji Joko  16 , Kojiro Michitaka  17 , Koichiro Miki  18   19 , Kazuhiro Takahashi  20 , Tatsuya Ide  21 , Shigetoshi Fujiyama  22 , Tomoko Kohno  23 , Hiroshi Itoh  23 , Sakiyo Tsukamoto  23 , Yuko Suzuki  23 , Yoshiaki Kawano  24 , Wataru Sugiura  25 , Hiromitsu Kumada  2
Affiliations
Clinical Trial

Switching from entecavir to tenofovir disoproxil fumarate for HBeAg-positive chronic hepatitis B patients: a phase 4, prospective study

Fumitaka Suzuki et al. BMC Gastroenterol. .

Abstract

Background: Tenofovir disoproxil fumarate (TDF) is widely used and recommended as first-line treatment for patients infected with the hepatitis B virus (HBV). However, current data are limited regarding the efficacy and safety of switching to TDF for the treatment of chronic hepatitis B in hepatitis B e-antigen (HBeAg)-positive patients who are virologically suppressed with another nucleos(t)ide analogue. The primary objective of this study was to evaluate the hepatitis B surface antigen (HBsAg) reduction potential of switching from entecavir (ETV) to TDF at week 48 in HBeAg-positive chronic hepatitis B patients with undetectable serum HBV-DNA.

Methods: In this multicenter, single-arm, open-label, phase 4 clinical study, 75 participants currently treated with ETV 0.5 mg once daily were switched to TDF 300 mg once daily for 96 weeks.

Results: At week 48, 3/74 participants (4%) achieved 0.25 log10 reduction of HBsAg levels from baseline (the primary endpoint). Mean HBsAg reduction was -0.14 log10 IU/mL and 12% (9/74) achieved 0.25 log10 reduction by 96 weeks. No participants achieved HBsAg seroclearance. HBsAg reduction at weeks 48 and 96 was numerically greater in participants with higher alanine aminotransferase levels (≥ 60 U/L). Seventeen participants (25%) achieved HBeAg seroclearance up to week 96. No participants experienced viral breakthrough. All drug-related adverse events (18 participants [24%]) were mild in intensity, including an increase in urine beta-2-microglobulin (15 participants [20%]).

Conclusions: In conclusion, HBsAg reduction was limited after switching from ETV to TDF in this study population. Further investigation is warranted to better understand the clinical impact of switching from ETV to TDF. ClinicalTrials.gov: NCT03258710 registered August 21, 2017. https://clinicaltrials.gov/ct2/show/NCT03258710?term=NCT03258710&draw=2&rank=1.

Keywords: Chronic hepatitis B; Entecavir; HBeAg-positive; HBsAg; Tenofovir disoproxil fumarate.

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Conflict of interest statement

This study (NCT03258710) was conducted with a research fund from GlaxoSmithKline (GSK), in which FS, YS1, YK1, TA, MA, MK1, TW, YT, ME, MK2, NM, HK1, KJ, KM1, KM2, KT, TI, HY, SF, and HK2 participated as investigators and their institutions received funding in relation to this work. FS has served on the advisory board for GSK, and has received personal fees from AbbVie Inc., Bristol Myers Squibb, and GSK; YT has served on several advisory boards for GSK, has received personal fees from Fujirebio Inc., GSK, and Sysmex Corporation, has received personal fees and grants from Gilead Sciences Inc. and grants from FUJIFILM Corporation and Janssen Pharmaceutical KK, and has served on the Board of Trustees of the Leland Stanford Junior University; MK1 and HY have served on the advisory board for GSK, and have received personal fees from GSK; TA has received grants and personal fees from AbbVie Inc.; MA has received grants and personal fees from AbbVie Inc., and Merck Sharp & Dohme (MSD); KJ has received speaking fees from AbbVie Inc., Gilead Sciences, Inc., MSD, and Otsuka Pharmaceutical Co., Ltd.; TK, HI, YS2, and YK2 are employees of and own stock in GSK; ST is employee of GSK; WS is a former employee of GSK; HK2 has served as a speaker and trainer for AbbVie Inc., Eisai Co. Ltd, Gilead Sciences, Inc., MSD KK, and Sumitomo Dainippon Pharma.

Figures

Fig. 1
Fig. 1
Participant disposition. AE, adverse event. aParticipants who received at least 1 dose of study treatment after enrollment. bExcludes participants who had no efficacy data at least 15 days after the start of study treatment
Fig. 2
Fig. 2
Mean change in HBsAg up to week 96 (FAS). FAS, full analysis set; HBsAg, hepatitis B surface antigen
Fig. 3
Fig. 3
Individual Responder Change in HBsAg and ALT (FAS). ALT, alanine aminotransferase; FAS, full analysis set; HBsAg, hepatitis B surface antigen; W, weeks
Fig. 4
Fig. 4
Individual participant observed clinical course types: change in B2MG (µg/g creatinine) and eGFR (mL/min/1.73m2). B2MG, urine beta-2-microglobulin; Cr, creatinine; eGFR, estimated glomerular filtration rate
See this image and copyright information in PMC

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