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Non-Inferior Efficacy of Tenofovir Disoproxil to Tenofovir Disoproxil Fumarate in Virologically Suppressed Chronic Hepatitis B Patients
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2022-09-23 , DOI: 10.2147/dddt.s376821 Hyung Joon Yim 1 , Ji Hoon Kim 2 , Yong Kyun Cho 3 , Young Oh Kweon 4 , Hyun Chin Cho 5 , Jae Seok Hwang 6 , Changhyeong Lee 7 , Moon Soo Koh 8 , Yang-Hyun Baek 9 , Young-Min Park 10 , Jeong-Hoon Lee 11 , Seung Up Kim 12 , Min-Kyu Kang 13 , Neung Hwa Park 14 , June Sung Lee 15 , Young Eun Chon 16 , Gab Jin Cheon 17 , Hee Bok Chae 18 , Joo Hyun Sohn 19 , Young-Suk Lim 20
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2022-09-23 , DOI: 10.2147/dddt.s376821 Hyung Joon Yim 1 , Ji Hoon Kim 2 , Yong Kyun Cho 3 , Young Oh Kweon 4 , Hyun Chin Cho 5 , Jae Seok Hwang 6 , Changhyeong Lee 7 , Moon Soo Koh 8 , Yang-Hyun Baek 9 , Young-Min Park 10 , Jeong-Hoon Lee 11 , Seung Up Kim 12 , Min-Kyu Kang 13 , Neung Hwa Park 14 , June Sung Lee 15 , Young Eun Chon 16 , Gab Jin Cheon 17 , Hee Bok Chae 18 , Joo Hyun Sohn 19 , Young-Suk Lim 20
Affiliation
Purpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet’s size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB).
Patients and Methods: CHB patients with HBV-DNA < 69 IU/mL after ≥ 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA < 69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.
Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was − 2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; − 0.8 ± 9.8 versus − 2.4 ± 12.8 mL/min, respectively (P=0.017).
Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.
Keywords: viral DNA, bone density, antiviral agents, viral suppression
中文翻译：
在病毒学抑制的慢性乙型肝炎患者中，替诺福韦酯与富马酸替诺福韦酯的非劣效疗效
目的：替诺福韦地索普西 (TD) 是从富马酸替诺福韦地索普西 (TDF) 改良而来的，被开发为无盐制剂，通过减小片剂的大小来去除富马酸盐以提高口服摄入的便利性。我们评估了慢性乙型肝炎（CHB）患者从 TDF 300 mg 转换后 TD 245 mg 抗病毒作用的维持情况和总体安全性。
患者和方法：纳入 TDF 治疗≥ 24 周后 HBV-DNA < 69 IU/mL 的慢性乙型肝炎患者。主要疗效终点是第 48 周时的 HBV-DNA 抑制率（HBV-DNA < 69 IU/mL）；我们在疗效方面评估了 TD 与 TDF 的非劣效性（10% 边缘）。根据不良事件 (AE)、实验室测试、骨矿物质密度和肾功能异常评估安全性。
结果：总体而言，189 名受试者以 2:1 的比例随机分组，TD 组和 TDF 组分别有 117 名和 66 名受试者完成了研究。在符合方案组中，TD 组和 TDF 组在第 48 周的 HBV-DNA 抑制率分别为 99.1% 和 100%。HBV-DNA 抑制率组间差异的 97.5% 单侧置信区间的下限为 - 2.8%，高于预先设定的非劣效性界值。从基线到第 48 周的肌酐清除率变化在 TD 组和 TDF 组中显着减少；− 0.8 ± 9.8 与 − 2.4 ± 12.8 mL/min 分别（P = 0.017）。
结论： TD在维持慢乙肝患者病毒抑制方面不劣于TDF，肾功能下降幅度较小。
关键词：病毒DNA，骨密度，抗病毒药物，病毒抑制
更新日期：2022-09-23
Patients and Methods: CHB patients with HBV-DNA < 69 IU/mL after ≥ 24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA < 69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities.
Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was − 2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; − 0.8 ± 9.8 versus − 2.4 ± 12.8 mL/min, respectively (P=0.017).
Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.
Keywords: viral DNA, bone density, antiviral agents, viral suppression
中文翻译：
在病毒学抑制的慢性乙型肝炎患者中，替诺福韦酯与富马酸替诺福韦酯的非劣效疗效
目的：替诺福韦地索普西 (TD) 是从富马酸替诺福韦地索普西 (TDF) 改良而来的，被开发为无盐制剂，通过减小片剂的大小来去除富马酸盐以提高口服摄入的便利性。我们评估了慢性乙型肝炎（CHB）患者从 TDF 300 mg 转换后 TD 245 mg 抗病毒作用的维持情况和总体安全性。
患者和方法：纳入 TDF 治疗≥ 24 周后 HBV-DNA < 69 IU/mL 的慢性乙型肝炎患者。主要疗效终点是第 48 周时的 HBV-DNA 抑制率（HBV-DNA < 69 IU/mL）；我们在疗效方面评估了 TD 与 TDF 的非劣效性（10% 边缘）。根据不良事件 (AE)、实验室测试、骨矿物质密度和肾功能异常评估安全性。
结果：总体而言，189 名受试者以 2:1 的比例随机分组，TD 组和 TDF 组分别有 117 名和 66 名受试者完成了研究。在符合方案组中，TD 组和 TDF 组在第 48 周的 HBV-DNA 抑制率分别为 99.1% 和 100%。HBV-DNA 抑制率组间差异的 97.5% 单侧置信区间的下限为 - 2.8%，高于预先设定的非劣效性界值。从基线到第 48 周的肌酐清除率变化在 TD 组和 TDF 组中显着减少；− 0.8 ± 9.8 与 − 2.4 ± 12.8 mL/min 分别（P = 0.017）。
结论： TD在维持慢乙肝患者病毒抑制方面不劣于TDF，肾功能下降幅度较小。
关键词：病毒DNA，骨密度，抗病毒药物，病毒抑制
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