用TAF治疗HBV治疗后骨丢失风险较低

StephenW

Bone loss risk lower after treatment with TAF vs. TDF for HBV

Seto WK, et al. Clin Gastroenterol Hepatol. 2018;doi:10.1016/j.cgh.2018.06.023.
July 2, 2018

Patients with hepatitis B showed continued improvement in bone safety after 2 years of treatment with tenofovir alafenamide compared with tenofovir disoproxil fumarate, according to a recently published study.

According to Wai-Kay Seto, MD, from the University of Hong Kong, and colleagues, tenofovir alafenamide (TAF) is more stable in plasma compared with tenofovir disoproxil fumarate (TDF), which enables more efficient delivery of the active form of tenofovir disphosphate to hepatocytes at a lower dose than TDF is traditionally prescribed.


“While TDF is highly efficacious monotherapy for [chronic HBV (CHB)], its use is associated with osteopenia and [bone mineral density (BMD)] loss,” Seto and colleagues wrote. “As the population of CHB patients requiring lifelong therapy ages, the potential exists for the long-term safety advantages of TAF therapy relative to TDF to be more fully realized.”

Seto and colleagues randomly assigned 1,298 patients with HBV to receive either TAF 25 mg (n = 866) or TDF 300 mg (n = 432) once daily for 96 to 144 weeks. The overall cohort included patients who were either HBV e antigen positive (n = 873) or negative (n = 425) and either treatment experienced or treatment naive.

Mean decrease in hip BMD was significantly less among the TAF group compared with the TDF group at week 48 (–0.16% vs. –1.86%; P < .001) and at week 96 (–0.33% vs. –2.51%; P < .001). Similarly, mean decrease in spine BMD was less in the TAF group at week 48 (–0.57% vs. –2.37%; P < .001) and week 96 (–0.75% vs. –2.57%; P < .001).

Among patients with higher risk for bone loss, the researchers observed a smaller proportion of patients who experienced a bone loss of more than 3% in hip BMD in the TAF group compared with the TDF group by subanalysis of risk factors including female sex (18% vs. 50%; P < .001), advanced age (20% vs. 52%; P < .001), Asian ethnicity (15% vs. 42%; P < .001) and baseline renal impairment (20% vs. 54%; P < .001). Results were similar for spine BMD changes.

Independent predictors for a decrease in hip BMD included TAF vs. TDF treatment (OR = 0.232; 95% CI, 0.17-0.317), no prior use of interferons (OR = 0.462; 95% CI, 0.295-0.723), age younger than 50 years vs. 50 years (OR = 0.619; 95% CI, 0.43-0.889), female vs. male sex (OR = 1.471; 95% CI, 1.065-2.032) and baseline renal impairment (OR = 0.991; 95% CI, 0.984-0.998).

“Taken together, our results support the concept that reduced systemic exposures of tenofovir may be responsible for the minimal changes in bone turnover and smaller declines in BMD observed in patients receiving TAF vs. those receiving TDF,” the researchers concluded. – by Talitha Bennett

Disclosure: Seto reports advisory or speaker positions with AbbVie, Bristol-Myers Squibb and Gilead. Please see the full study for the other authors’ relevant financial disclosures

StephenW

用TAF治疗HBV治疗后骨丢失风险较低

Seto WK，et al。 Clin Gastroenterol Hepatol。 2018; DOI：10.1016 / j.cgh.2018.06.023。
2018年7月2日

根据最近发表的一项研究，与使用替诺福韦地索普西富马酸盐相比，接受替诺福韦艾拉酚胺治疗2年后，乙型肝炎患者的骨安全性持续改善。

来自香港大学的Wai-Kay Seto博士及其同事表示，与替诺福韦地索普西富马酸盐（TDF）相比，替诺福韦艾拉酚胺（TAF）在血浆中更稳定，可以更有效地递送活性形式的替诺福韦二磷酸盐传统上规定以比TDF更低剂量的肝细胞。


“虽然TDF是[慢性HBV（CHB）]的高效单药治疗，但它的使用与骨质减少和[骨矿物质密度（BMD）]损失有关，”Seto及其同事写道。 “由于需要终身治疗的CHB患者人群年龄增长，TAF治疗相对于TDF的长期安全优势可能会更加充分地实现。”

Seto及其同事随机分配了1,298例HBV患者，每天一次接受TAF 25 mg（n = 866）或TDF 300 mg（n = 432），持续96至144周。整个队列包括HBV e抗原阳性（n = 873）或阴性（n = 425）且经历过治疗或未经治疗的患者。

在第48周时，TAF组与TDF组相比，髋部骨密度平均下降明显减少（-0.16％vs。-1.86％; P <.001）和第96周（-0.33％vs。-2.51％; P <.001）。同样，第48周TAF组脊柱BMD平均下降较少（-0.57％vs。-2.37％; P <.001）和96周（-0.75％vs。-2.57％; P <.001）。

在骨丢失风险较高的患者中，研究人员观察到，通过对包括女性在内的风险因素进行亚组分析，TAF组髋部BMD骨丢失率超过3％的患者比例较小（18％） 50％; P <.001），高龄（20％vs。52％; P <.001），亚洲种族（15％vs。42％; P <.001）和基线肾功能损害（20％vs 54％; P <.001）。脊柱骨密度变化的结果相似。

髋部骨密度降低的独立预测因素包括TAF与TDF治疗（OR = 0.232; 95％CI，0.17-0.317），之前未使用干扰素（OR = 0.462; 95％CI，0.295-0.723），年龄小于50年与50年（OR = 0.619; 95％CI，0.43-0.889），女性与男性（OR = 1.471; 95％CI，1.065-2.032）和基线肾功能损害（OR = 0.991; 95％CI ，0.984-0.998）。

“总的来说，我们的结果支持这样的概念，即减少替诺福韦的全身暴露可能是造成骨转换的微小变化和接受TAF的患者与接受TDF的患者BMD下降幅度较小的原因，”研究人员得出结论。 - Talitha Bennett

披露：Seto报告了AbbVie，Bristol-Myers Squibb和Gilead的咨询或发言人职位。有关其他作者的相关财务披露，请参阅完整的研究