Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

  • Aliment Pharmacol Ther. 2021 Nov;54(9):1134-1149. doi: 10.1111/apt.16611.
Zhihong Liu  1 ,  Qinglong Jin  2 ,  Yuexin Zhang  3 ,  Guozhong Gong  4 ,  Guicheng Wu  5 ,  Lvfeng Yao  6 ,  Xiaofeng Wen  7 ,  Zhiliang Gao  1 ,  Yan Huang  4 ,  Daokun Yang  8 ,  Enqiang Chen  9 ,  Qing Mao  5 ,  Shide Lin  10 ,  Jia Shang  11 ,  Huanyu Gong  4 ,  Lihua Zhong  12 ,  Huafa Yin  13 ,  Fengmei Wang  14 ,  Peng Hu  5 ,  Ling Xiao  15 ,  Chuan Li  15 ,  Qiong Wu  15 ,  Chang'an Sun  15 ,  Junqi Niu  2 ,  Jinlin Hou  1 ,  TMF Study Group
Affiliations
  • 1. Guangzhou, China.
  • 2. Changchun, China.
  • 3. Urumchi, China.
  • 4. Changsha, China.
  • 5. Chongqing, China.
  • 6. Fuzhou, China.
  • 7. Liuzhou, China.
  • 8. Xinxiang, China.
  • 9. Chengdu, China.
  • 10. Zunyi, China.
  • 11. Zhengzhou, China.
  • 12. Harbin, China.
  • 13. Hefei, China.
  • 14. Tianjin, China.
  • 15. Lianyungang, China.
PMID: 34587302 DOI: 10.1111/apt.16611
Abstract

Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF).

Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB).

Methods: We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities.

Results: We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups.

Conclusion: TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

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