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 作者: StephenW 时间: 2018-7-3 13:12
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。