Bone Health and Osteoporosis Center, College of Medicine, University of Cincinnati, 222 Piedmont Avenue, Suite 6300, Cincinnati, OH 45219, USA.
Osteoporos Int. 2012 Jan;23(1):327-37. doi: 10.1007/s00198-011-1755-2. Epub 2011 Sep 3.
Serious adverse events of infections that occurred in subjects receiving denosumab or placebo in the Fracture Reduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were examined in detail. Serious adverse events of infections in denosumab subjects had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab.
Denosumab reduces the risk for new vertebral, hip, and nonvertebral fractures compared with placebo. In the pivotal phase 3 fracture trial (FREEDOM), the overall safety profile and incidence of adverse events including adverse events of infections were similar between groups. Serious adverse events of erysipelas and cellulitis were more frequent in denosumab-treated subjects. In this report, we further evaluate the details of infectious events in FREEDOM to better understand if RANKL inhibition with denosumab influences infection risk.
FREEDOM was an international multicenter, randomized, double-blind, placebo-controlled study in postmenopausal women with osteoporosis randomly assigned to receive placebo (n = 3,906) or denosumab 60 mg every 6 months (n = 3,902). The incidence of adverse events and serious adverse events categorized within the Medical Dictionary for Regulatory Activities system organ class, "Infections and Infestations," was compared between the placebo and denosumab groups by body systems and preferred terms. The temporal relationship between occurrence of serious adverse events of infections of interest and administration of denosumab was explored.
Serious adverse events of infections involving the gastrointestinal system, renal and urinary system, ear, and endocarditis were numerically higher in the denosumab group compared with placebo, but the number of events was small. No relationship was observed between serious adverse events of infections and timing of administration or duration of exposure to denosumab.
Serious adverse events of infections that occurred with denosumab treatment had heterogeneous etiology, with no clear clinical pattern to suggest a relationship to time or duration of exposure to denosumab.
在每 6 个月评估地舒单抗治疗骨质疏松症骨折减少的 FREEDOM 研究中，详细检查了接受地舒单抗或安慰剂的受试者发生的感染严重不良事件。地舒单抗组感染严重不良事件的病因具有异质性，没有明确的临床模式表明与地舒单抗的暴露时间或持续时间有关。
与安慰剂相比，地舒单抗可降低新发椎体、髋部和非椎体骨折的风险。在关键性 3 期骨折试验（FREEDOM）中，两组的总体安全性概况和不良事件发生率（包括感染不良事件）相似。地舒单抗治疗组的丹毒和蜂窝织炎严重不良事件更为常见。在本报告中，我们进一步评估 FREEDOM 中感染事件的细节，以更好地了解 RANKL 抑制对地舒单抗是否会影响感染风险。
FREEDOM 是一项国际性、多中心、随机、双盲、安慰剂对照研究，纳入了绝经后骨质疏松症女性，随机分配至安慰剂（n = 3906）或地舒单抗 60mg 每 6 个月（n = 3902）组。通过医疗保健相关术语系统器官分类（MedDRA），比较了安慰剂组和地舒单抗组中不良事件和严重不良事件的发生率，包括系统器官分类“感染和侵染”和首选术语。探讨了发生感染严重不良事件与地舒单抗给药之间的时间关系。
地舒单抗组胃肠道系统、肾脏和泌尿系统、耳部和心内膜炎感染严重不良事件的发生率高于安慰剂组，但事件数量较少。未观察到感染严重不良事件与地舒单抗的给药时间或暴露时间之间存在关系。
地舒单抗治疗相关感染严重不良事件的病因具有异质性，没有明确的临床模式表明与地舒单抗的暴露时间或持续时间有关。
