对FRAME和ARCH的事后分析显示,在最初接受romosozumab与安慰剂或阿仑膦酸钠治疗的女性中,研究中的12个月前的非椎骨和椎骨骨折较少见。romosozumab治疗患者的复发性骨折风险也较低,并且没有骨折相关的并发症。结果支持骨折后继续进行romosozumab治疗。
目的:事后分析评估romosozumab的疗效和安全性,在骨折后即刻施用,在FRAME和ARCH阶段3试验中。
方法:在FRAME(NCT01575834)和ARCH(NCT01631214)中,绝经后骨质疏松症妇女随机分为1:1,每月服用罗莫索珠单抗210mg或比较(FRAME,安慰剂;ARCH,阿仑膦酸钠每周70毫克)持续12个月,其次是抗吸收治疗(FRAME,denosumab;ARCH,阿仑膦酸盐)。在12个月之前经历研究中的非椎骨或新的/恶化的椎骨骨折的患者中,我们报告了以下情况:骨折和治疗引起的不良事件(TEAE)发生率,直到36个月,骨矿物质密度变化(BMD),和romosozumab时机。由于采用的样本量,在治疗之间进行有意义的统计学比较是不可能的.
结果:到第12个月,研究中的非椎骨和椎骨骨折的发生率在数值上低于接受比较治疗的患者(FRAME,1.6%和0.5%对2.1%和1.6%;ARCH,3.4%和3.3%对4.6%和4.9%,分别)。在12个月前经历研究中的非椎骨骨折的患者中,最初接受romosozumab治疗的患者的复发性非椎骨和随后的椎骨骨折发生率在数字上较低(FRAME,3.6%[2/56]和1.8%[1/56],9.2%[7/76]和3.9%[3/76];ARCH,10.0%[7/70]和5.7%[4/70]对12.6%[12/95]和8.4%[8/95],分别)。在12个月前研究中的椎骨骨折患者中,romosozumab与比较器相比,复发性椎骨和随后的非椎骨骨折发生率在数值上较低(FRAME,0.0%[0/17]和0.0%[0/17]对11.9%[7/59]和8.5%[5/59];ARCH,9.0%[6/67]和7.5%[5/67]对15.0%[15/100]和16.0%[16/100],分别)。在12个月前骨折患者中,接受romosozumab治疗的患者未报告骨折相关并发症。romosozumab的BMD增益在数值上大于比较物。
结论:数据表明支持骨折后继续使用romosozumab治疗的有效性和安全性。
背景:NCT01575834;NCT01631214。
Post hoc analysis of FRAME and ARCH revealed that on-
study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab‑treated patients, and there were no fracture‑related complications. Results support continuing romosozumab treatment post‑fracture.
OBJECTIVE: Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials.
METHODS: In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-
study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible.
RESULTS: Incidence of on-
study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-
study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-
study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracture‑related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators.
CONCLUSIONS: Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture.
BACKGROUND: NCT01575834; NCT01631214.