Liu Zhihong, Jin Qinglong, Zhang Yuexin, Gong Guozhong, Wu Guicheng, Yao Lvfeng, Wen Xiaofeng, Gao Zhiliang, Huang Yan, Yang Daokun, Chen Enqiang, Mao Qing, Lin Shide, Shang Jia, Gong Huanyu, Zhong Lihua, Yin Huafa, Wang Fengmei, Hu Peng, Wu Qiong, Pan Chao, Jia Wen, Li Chuan, Sun Chang'an, Niu Junqi, Hou Jinlin
Department of Infectious Diseases and Hepatology Unit, Institutes of Liver Diseases Research of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
The First Hospital of Jilin University, Changchun, Jilin, China.
J Clin Transl Hepatol. 2023 Jun 28;11(3):649-660. doi: 10.14218/JCTH.2022.00058. Epub 2022 Nov 1.
Tenofovir amibufenamide (TMF) is a novel phosphoramidated prodrug of tenofovir with noninferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate (TDF) in 48 weeks of treatment. Here, we update 96-week comparison results.
Patients with chronic hepatitis B were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks. The virological suppression was defined as HBV DNA levels <20 IU/mL at week 96. Safety was evaluated thoroughly with focusing on bone, renal, and metabolic parameters.
Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative populations. Noninferior efficacy was maintained in the pooled population, while it was first achieved in patients with HBV DNA ≥7 or 8 log10 IU/mL at baseline. Non-indexed estimated glomerular filtration rate for renal safety assessment was adopted, while a smaller decline of which was seen in the TMF group than in the TDF group (=0.01). For bone mineral density, patients receiving TMF displayed significantly lower reduction levels in the densities of spine, hip, and femur neck at week 96 than those receiving TDF. In addition, the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite trend.
TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles (NCT03903796).
替诺福韦氨苯砜（TMF）是一种新型的替诺福韦磷酰胺前药，在48周的治疗中，其疗效不劣于富马酸替诺福韦二吡呋酯（TDF），且对骨骼和肾脏的安全性更好。在此，我们更新了96周的比较结果。
慢性乙型肝炎患者按2:1分配，接受25 mg TMF或300 mg TDF加匹配的安慰剂治疗96周。病毒学抑制定义为第96周时HBV DNA水平<20 IU/mL。重点关注骨骼、肾脏和代谢参数，对安全性进行全面评估。
在HBeAg阳性和HBeAg阴性人群中，TMF组和TDF组在第96周时的病毒学抑制率相似。在汇总人群中维持了不劣效的疗效，而在基线时HBV DNA≥7或8 log10 IU/mL的患者中首次实现。采用非指标性估计肾小球滤过率进行肾脏安全性评估，TMF组的下降幅度小于TDF组（P=0.01）。对于骨密度，接受TMF治疗的患者在第96周时脊柱、髋部和股骨颈密度的降低水平明显低于接受TDF治疗的患者。此外，所有组在第48周后血脂参数稳定，而体重变化仍呈相反趋势。
与TDF相比，TMF在第96周时维持了相似的疗效，并继续具有更好的骨骼和肾脏安全性（NCT03903796）。
