3-year Treatment of Tenofovir Alafenamide vs. Tenofovir Disoproxil Fumarate for Chronic HBV Infection in China

Jinlin Hou, Qin Ning, Zhongping Duan, You Chen, Qing Xie, Fu-Sheng Wang, Lunli Zhang, Shanming Wu, Hong Tang, Jun Li, Feng Lin, Yongfeng Yang, Guozhong Gong, John F Flaherty, Anuj Gaggar, Shuyuan Mo, Cong Cheng, Gregory Camus, Chengwei Chen, Yan Huang, Jidong Jia, Mingxiang Zhang, GS-US-320-0110 and GS-US-320-0108 China Investigators, Jinlin Hou, Qin Ning, Zhongping Duan, You Chen, Qing Xie, Fu-Sheng Wang, Lunli Zhang, Shanming Wu, Hong Tang, Jun Li, Feng Lin, Yongfeng Yang, Guozhong Gong, John F Flaherty, Anuj Gaggar, Shuyuan Mo, Cong Cheng, Gregory Camus, Chengwei Chen, Yan Huang, Jidong Jia, Mingxiang Zhang, GS-US-320-0110 and GS-US-320-0108 China Investigators

Abstract

Background and aims: Tenofovir alafenamide (TAF) has similar efficacy to tenofovir disoproxil fumarate (TDF) but with improved renal and bone safety in chronic hepatitis B patients studied outside of China. We report 3-year results from two phase 3 studies with TAF in China (Clinicaltrials.gov: NCT02836249 and NCT02836236).

Methods: Chinese hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks (3 years). Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.

Results: Of the 334 patients (180 HBeAg-positive and 154 HBeAg-negative) randomized and treated, baseline characteristics were similar between groups. The overall mean age was 38 years and 73% were male. The mean HBV DNA was 6.4 log10 IU/mL. The median alanine aminotransferase was 88 U/L, and 37% had a history of antiviral use. At week 144, the proportion with HBV DNA <29 IU/mL was similar among the two groups, with TAF at 83% vs. TDF at 79%, and TAF at 93% vs. TDF at 92% for the HBeAg-positive and -negative patients, respectively. In each study, higher proportions of TAF than TDF patients showed normalized alanine aminotransferase (via the American Association for the Study of Liver Diseases and the China criteria) and showed loss of HBsAg; meanwhile, the HBeAg seroconversion rates were similar. Treatment was well-tolerated among the TAF patients, who showed a smaller median decline in creatinine clearance (-0.4 vs. -3.2 mL/min; p=0.014) and less percentage change in bone mineral density vs. TDF at hip (-0.95% vs. -1.93%) and spine (+0.35% vs. -1.40%).

Conclusions: In chronic hepatitis B patients from China, TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.

Keywords: Antiviral therapy; Bone safety; Chronic hepatitis B virus; Renal safety.

Conflict of interest statement

Jinlin Hou has served as a consultant for AbbVie, Arbutus, Bristol Myers Squibb, Gilead Sciences, Johnson & Johnson, Roche and received grants from Bristol Myers Squibb, Gilead, and Johnson & Johnson. Qin Ning has served as a consultant for Gilead Sciences, Johnson & Johnson, AbbVie, Roche, Bristol-Myers Squibb, MSD, and has received research funding from Bristol-Myers Squibb, Roche, and Gilead Sciences. Qing Xie has served as a consultant for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Johnson & Johnson, and Roche, and has received grants from Gilead Sciences. Shanming Wu has served as a consultant for Gilead Sciences, AbbVie, GSK, Bristol-Myers Squibb, and MSD, and has received research funding from Bristol-Myers Squibb, Roche, AbbVie, and Gilead Sciences. Hong Tang has served as a consultant for Gilead Sciences, MSD, AbbVie, GSK, Bristol-Myers Squibb, and has received research funding from Bristol-Myers Squibb, Roche, and Gilead Sciences. Jun Li has served as a consultant for Gilead, MSD, AbbVie, GSK, and Bristol-Myers Squibb. John F. Flaherty, Anuj Gaggar, Gregory Camus, Cong Cheng, and Shuyuan Mo are employees and stockholders of Gilead Sciences. Chengwei Chen has served as a consultant for Gilead, AbbVie, GSK, Bristol-Myers Squibb, MSD and received research funds from Bristol-Myers Squibb, Roche, AbbVie, and Gilead. Jidong Jia has served as a consultant for Abbvie, Bristol-Myers Squibb, Gilead and GSK, and received research funds from Bristol-Myers Squibb and Gilead. The other authors have no conflict of interests related to this publication.

© 2021 Authors.

Figures

Fig. 1. Viral suppression (HBV DNA
Fig. 1. Viral suppression (HBV DNA
(A) Proportions of HBeAg-positive patients with HBV DNA

Fig. 2. ALT normalization by visit week…

Fig. 2. ALT normalization by visit week using 2018 AASLD criteria.

(A) Proportions of HBeAg-positive…

Fig. 2. ALT normalization by visit week using 2018 AASLD criteria.
(A) Proportions of HBeAg-positive patients that achieved ALT normalization. (B) Proportions of HBeAg-negative patients that achieved ALT normalization. Analysis is missing equals failure and includes only patients with baseline ALT above the upper limit of normal for 2018 AASLD criteria (25 U/L and 35 U/L for males and females, respectively).

Fig. 3. Mean percentage changes in BMD.

Fig. 3. Mean percentage changes in BMD.

(A) Mean percentage change from baseline in hip…

Fig. 3. Mean percentage changes in BMD.
(A) Mean percentage change from baseline in hip BMD at weeks 24, 48, 72, 96, 120, and 144 of treatment in the subset of patients that underwent DXA scanning. (B) Mean percentage change from baseline in spine BMD at weeks 24, 48, 72, 96, 120, and 144 of treatment in the subset of patients that underwent DXA scanning. Analysis is missing equals excluded (observed data).
Fig. 2. ALT normalization by visit week…
Fig. 2. ALT normalization by visit week using 2018 AASLD criteria.
(A) Proportions of HBeAg-positive patients that achieved ALT normalization. (B) Proportions of HBeAg-negative patients that achieved ALT normalization. Analysis is missing equals failure and includes only patients with baseline ALT above the upper limit of normal for 2018 AASLD criteria (25 U/L and 35 U/L for males and females, respectively).
Fig. 3. Mean percentage changes in BMD.
Fig. 3. Mean percentage changes in BMD.
(A) Mean percentage change from baseline in hip BMD at weeks 24, 48, 72, 96, 120, and 144 of treatment in the subset of patients that underwent DXA scanning. (B) Mean percentage change from baseline in spine BMD at weeks 24, 48, 72, 96, 120, and 144 of treatment in the subset of patients that underwent DXA scanning. Analysis is missing equals excluded (observed data).

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Source: PubMed

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