Long-term efficacy and safety of tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B: 5-year results

Xieer Liang, Zhiliang Gao, Qing Xie, Jiming Zhang, Jifang Sheng, Jun Cheng, Chengwei Chen, Qing Mao, Wei Zhao, Hong Ren, Deming Tan, Junqi Niu, Shijun Chen, Chen Pan, Hong Tang, Hao Wang, Yimin Mao, Jidong Jia, Qin Ning, Min Xu, Shanming Wu, Jun Li, Xinxin Zhang, Wenyan Zhang, Cui Xiong, Jinlin Hou, Xieer Liang, Zhiliang Gao, Qing Xie, Jiming Zhang, Jifang Sheng, Jun Cheng, Chengwei Chen, Qing Mao, Wei Zhao, Hong Ren, Deming Tan, Junqi Niu, Shijun Chen, Chen Pan, Hong Tang, Hao Wang, Yimin Mao, Jidong Jia, Qin Ning, Min Xu, Shanming Wu, Jun Li, Xinxin Zhang, Wenyan Zhang, Cui Xiong, Jinlin Hou

Abstract

Background and aim: Long-term treatment with tenofovir disoproxil fumarate (TDF) has demonstrated suppression of viral replication outside of China. This study aims to assess efficacy, resistance and safety of TDF for up to 240 weeks in Chinese patients with chronic hepatitis B virus (HBV) infection.

Methods: Patients (HBeAg-positive or HBeAg-negative) who were randomised to receive TDF 300 mg or adefovir dipivoxil (ADV) 10 mg once daily in the 48-week double-blind phase (N = 498) were eligible to enter the open-label TDF phase (TDF-TDF and ADV-TDF groups) for additional 192 weeks.

Results: Overall, 457/512 (89.3%) randomised patients completed 240 weeks of treatment. Virological suppression was achieved in 84.5% and 87.9% in HBeAg-positive patients and 89.6% and 89.5% in HBeAg-negative patients in TDF-TDF and ADV-TDF groups, respectively, at week 240. The majority of patients from both groups had normalized alanine transaminase levels. More patients had HBeAg loss (41.7% vs. 36.4%) and HBeAg seroconversion (32.0% vs. 28.3%) in TDF-TDF than in ADV-TDF group, respectively. Only one HBeAg-positive patient in TDF-TDF group had HBsAg loss at week 240. No evidence of resistance to TDF was observed. The incidence of adverse events was similar in both groups (TDF-TDF, 56.4% vs. ADV-TDF, 51.6%). One patient had serum creatinine elevation ≥ 0.5 mg/dL above baseline, and three patients had confirmed grade 3/4 phosphorus abnormalities (< 2 mg/dL).

Conclusion: In Chinese patients with chronic HBV, long-term treatment with TDF showed sustained viral suppression without development of resistance up to 240 weeks. No new safety concerns were found with TDF in this patient population. Clinical Trial Registration ClinicalTrial.gov Identifier NCT01300234; GSK Clinical Study Register 114648.

Keywords: Antiviral therapy; Chronic hepatitis B; Long-term tenofovir disoproxil fumarate; Virological suppression.

Conflict of interest statement

Jinlin Hou has received consulting fees and grant/research support from Bristol-Myers Squibb, GlaxoSmithKline, Novartis and Roche. Qin Ning has received consulting fees and grant/research support from Bristol-Myers Squibb, GlaxoSmithKline, MSD, Novartis and Roche. Wenyan Zhang and Cui Xiong are employees of GlaxoSmithKline. All other authors have no conflict of interest to disclose.

Figures

Fig. 1
Fig. 1
Patient disposition. ADV, adefovir dipivoxil; o.d., once daily; TDF, tenofovir disoproxil fumarate. †Three patients randomised to adefovir 10 mg group did not receive study treatment; hence, total safety and intent-to-treat population was N = 509
Fig. 2
Fig. 2
Proportion of patients with HBV DNA a HBeAg-positive, b HBeAg-negative. ADV, adefovir dipivoxil; HBV, hepatitis B virus; ITT, intent-to-treat; TDF, tenofovir disoproxil fumarate. †Data on file of global phase III pivotal studies [2, 5]
Fig. 3
Fig. 3
Proportion of HVL and non-HVL patients with HBV DNA n = 82) and non-HVL (n = 427)

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