Summary

In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density.

Introduction

In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study.

Methods

In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME.

Results

In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups.

Conclusions

Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.

中文翻译：

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Romosozumab 在参加 FRAME 试验的欧洲患者中的疗效和安全性

概括

在这项事后分析中，我们评估了 romosozumab 在参加 FRAME 的欧洲患者中的疗效和安全性。Romosozumab 治疗 12 个月，然后再使用 denosumab 24 个月，导致主要骨折类别的早期和持续风险降低，与骨矿物质密度的大幅增加有关。

介绍

在 romosozumab 用于绝经后骨质疏松症妇女的多国 FRAME 3 期试验中，观察到中美洲和南美洲患者与世界其他地区的临床和非椎体骨折结局之间存在显着差异。这项事后分析评估了 romosozumab 在参加 FRAME 试验和扩展研究的欧洲患者中的疗效和安全性。

方法

在 FRAME (NCT01575834) 中，患者以 1:1 的比例随机分配至 romosozumab 210 mg 或安慰剂每月 (QM) 治疗 12 个月，然后是开放标签 denosumab 60 mg Q6M 至第 36 个月，包括一项为期 12 个月的延长研究。我们报告了参加 FRAME 的欧洲患者的主要骨折结局发生率、骨矿物质密度 (BMD) 相对于基线的变化和安全性。

结果

在 FRAME 中，3013/7180 (41.96%) 名患者是欧洲人；1494 人接受了 romosozumab，1519 人接受了安慰剂。通过 12 个月，romosozumab 与安慰剂相比降低了非椎体骨折（1.4% 对 3.0%；p  = 0.004）、临床骨折（1.4% 对 3.6%；p  < 0.001）、新椎体骨折（0.4% 对 2.1%）的骨折风险；p  < 0.001）和严重骨质疏松性骨折（0.9% 对 2.8%；p  < 0.001），结果在过渡到狄诺塞麦后持续 36 个月。在第 12 个月，使用 romosozumab 可减少髋部骨折的数量（0.2% 对 0.6%；p = 0.092)。与安慰剂相比，Romosozumab 在第 12 个月时增加了 BMD；romosozumab 和安慰剂组的所有患者在过渡到地诺单抗后的第 36 个月都经历了进一步的增加。各组之间的不良事件是平衡的。

结论

在 FRAME 的欧洲患者中，romosozumab 导致所有主要骨折类别的早期和持续风险降低，与过渡到地诺单抗后持续的大量 BMD 增加相关。