Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, UK.
Centre for Integrated Research in Musculoskeletal Ageing (CIMA), Mellanby Centre for Bone Research, University of Sheffield, Sheffield, UK.
Osteoporos Int. 2021 Aug;32(8):1601-1608. doi: 10.1007/s00198-020-05815-0. Epub 2021 Feb 3.
This study aimed to determine the interaction between baseline FRAX fracture probability and romosozumab efficacy. Using an ITT approach, it was determined that the efficacy of romosozumab on clinical fracture, osteoporotic fracture, and major osteoporotic fracture is significantly greater in patients at high baseline fracture risk, when compared with placebo.
Post hoc analyses of placebo-controlled osteoporosis treatment studies have shown significantly greater reductions of fracture incidence for higher fracture risk patients. This study determined the interaction between baseline FRAX fracture probability and romosozumab efficacy in the placebo-controlled first year of the phase 3 FRAME study (NCT01575834).
Using an ITT approach, an extension of Poisson regression analysis studied the relationship between treatment, FRAX 10-year probability of major osteoporotic fracture (MOF, calculated without BMD) and risk of first incident fracture (adjusting for age and follow-up time). Treatment interactions considered outcomes of all clinical fractures, osteoporotic fractures, MOF, clinical vertebral fractures, and morphometric vertebral fractures. Two-sided p value of < 0.1 for the interaction between treatment and FRAX was considered significant.
Compared with placebo, romosozumab reduced the incidence of all fracture outcomes in the first year (range: 32% reduction in MOF [p = 0.07] to 80% reduction in clinical vertebral fractures [p = 0.038]). Significant interactions were observed between efficacy and baseline FRAX probability for composite outcomes of clinical fractures, osteoporotic fractures, and MOF (p = 0.064-0.084), but not vertebral fractures (p > 0.3). For example, romosozumab decreased all clinical fractures by 22% at the 25th centile of FRAX probability but the reduction was 41% at the 75th centile. Exclusion of vertebral fractures from each composite fracture outcome (i.e. only nonvertebral fractures included) showed even stronger interactions with baseline FRAX probability (p = 0.036-0.046).
Efficacy of romosozumab on clinical fracture, osteoporotic fracture, and MOF is significantly greater in patients at high baseline fracture risk compared with placebo.
本研究旨在确定基线 FRAX 骨折概率与 romosozumab 疗效之间的相互作用。采用意向治疗（ITT）方法，与安慰剂相比，在基线骨折风险较高的患者中，romosozumab 对临床骨折、骨质疏松性骨折和主要骨质疏松性骨折的疗效显著更高。
对安慰剂对照骨质疏松治疗研究的事后分析表明，对于高骨折风险患者，骨折发生率的降低幅度显著更大。本研究采用 ITT 方法，对 3 期 FRAME 研究（NCT01575834）的安慰剂对照第 1 年进行了 FRAX 骨折概率与 romosozumab 疗效之间的扩展泊松回归分析。
采用 ITT 方法，通过治疗、不包括 BMD 的 FRAX 10 年主要骨质疏松性骨折（MOF）概率和首次骨折事件风险（根据年龄和随访时间调整）的扩展泊松回归分析，研究治疗与 FRAX 之间的关系。考虑到治疗相互作用的所有临床骨折、骨质疏松性骨折、MOF、临床椎体骨折和形态计量椎体骨折。治疗与 FRAX 之间的交互作用，双侧 p 值＜0.1 被认为具有统计学意义。
与安慰剂相比，romosozumab 在第 1 年降低了所有骨折结局的发生率（范围：MOF 降低 32%[p = 0.07]，临床椎体骨折降低 80%[p = 0.038]）。在临床骨折、骨质疏松性骨折和 MOF 的复合结局方面，观察到疗效与基线 FRAX 概率之间存在显著交互作用（p = 0.064-0.084），但在椎体骨折方面没有交互作用（p＞0.3）。例如，在 FRAX 概率的 25 百分位数时，romosozumab 降低所有临床骨折的发生率为 22%，而在 75 百分位数时，降低的发生率为 41%。从每个复合骨折结局中排除椎体骨折（即仅包括非椎体骨折）显示出与基线 FRAX 概率更强的相互作用（p = 0.036-0.046）。
与安慰剂相比，在基线骨折风险较高的患者中，romosozumab 对临床骨折、骨质疏松性骨折和 MOF 的疗效显著更高。
