Objective: In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks. Methods: Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated. Results: 666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion: CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).
目的： 研究艾米替诺福韦（TMF）治疗144周或富马酸替诺福韦酯（TDF）经治慢性乙型肝炎（CHB）患者换用TMF治疗48周后的安全性结果。 方法： CHB患者按2∶1比例随机分配到TMF初治组（25 mg）或TDF转换组（300 mg），并在前96周接受TMF对比TDF的双盲双模拟治疗。在96～144周期间，所有患者均接受48周的开放标签TMF治疗，并对肾脏、骨骼、代谢、体质量等进行安全性评估。 结果： TMF初治组和TDF转换组分别有666例和336例患者接受了试验药物。截至第144周，TMF治疗的安全性良好；在第96～144周期间，两组总体安全性相似。在接受转换治疗后，TDF转换组的肾小球滤过率（使用非参数CKD-EPI公式计算）和肌酐清除率（使用Cockcroft Gault公式计算）较第96周分别升高（2.31±8.33）ml/min和（4.24±13.94）ml/min，显著高于TMF初治组的（0.91±8.06）ml/min和（1.30±13.94）ml/min；TDF转换组的髋部和脊柱骨密度（BMD）分别较第96周升高0.75%和1.41%，显著高于TMF初治组的-0.02%±3.57%；第144周TDF转换组累计的BMD显著降低事件发生率为20.1%，仍显著高于TMF初治组（12.7%）；TDF转换组总胆固醇/高密度脂蛋白胆固醇比值较第96周升高的中位数为0.16（0.00，0.43），显著高于TMF初治组的0.01（－0.17，0.31）；TDF转换组体质量指数较第96周升高（0.54±0.98）kg/m2，显著高于TMF初治组的（0.05±0.94）kg/m2。 结论： CHB患者接受144周TMF治疗的总体安全性良好。在接受转换治疗后，TDF转换组的肾脏和骨骼安全性得到显著改善，但同时也存在轻度的血脂和体质量增加（NCT03903796）。.