Anabolic therapies, recommended for patients at very high fracture risk, are administered subcutaneously (SC). The objective of this study was to evaluate the efficacy and safety of the abaloparatide microstructured transdermal system (abaloparatide-sMTS) as an alternative to the SC formulation. This phase 3, noninferiority study (NCT04064411) randomly assigned postmenopausal women with osteoporosis (N = 511) 1:1 to open-label abaloparatide administered daily via abaloparatide-sMTS or SC injection for 12 months. The primary comparison between treatment groups was the percentage change in lumbar spine bone mineral density (BMD) at 12 months, with a noninferiority margin of 2.0%. Secondary endpoints included percentage change in total hip and femoral neck BMD, bone turnover markers, dermatologic safety, and new clinical fracture incidence. At 12 months, percentage increase from baseline in lumbar spine BMD was 7.14% (SE: 0.46%) for abaloparatide-sMTS and 10.86% (SE: 0.48%) for abaloparatide-SC (treatment difference: −3.72% [95% confidence interval: −5.01%, −2.43%]). Percentage change in total hip BMD was 1.97% for abaloparatide-sMTS and 3.70% for abaloparatide-SC. Median changes from baseline at 12 months in serum procollagen type I N-terminal propeptide (s-PINP) were 52.6% for abaloparatide-sMTS and 74.5% for abaloparatide-SC. Administration site reactions were the most frequently reported adverse events (abaloparatide-sMTS, 94.4%; abaloparatide-SC, 70.5%). Incidence of serious adverse events was similar between groups. Mild or moderate skin reactions occurred with abaloparatide-sMTS with no identifiable risk factors for sensitization reactions. Few new clinical fractures occurred in either group. Noninferiority of abaloparatide-sMTS to abaloparatide-SC for percentage change in spine BMD at 12 months was not demonstrated; however, clinically meaningful increases from baseline in lumbar spine and total hip BMD were observed in both treatment groups. © 2023 Radius Health, Inc and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

中文翻译：

---

透皮 Abaloparatide 对患有骨质疏松症的绝经后妇女的疗效和安全性：一项随机研究

建议骨折风险极高的患者进行皮下注射 (SC) 的合成代谢疗法。本研究的目的是评估 abaloparatide 微结构透皮系统 (abaloparatide-sMTS) 作为 SC 制剂替代品的功效和安全性。这项 3 期非劣效性研究 (NCT04064411) 将患有骨质疏松症的绝经后女性 ( N  = 511) 以 1:1 的比例随机分配至开放标签 abaloparatide，每日通过 abaloparatide-sMTS 或 SC 注射给药，持续 12 个月。治疗组之间的主要比较是 12 个月时腰椎骨矿物质密度 (BMD) 的百分比变化，非劣效界为 2.0%。次要终点包括全髋关节和股骨颈 BMD 的百分比变化、骨转换标志物、皮肤科安全性和新的临床骨折发生率。12 个月时，abaloparatide-sMTS 腰椎 BMD 较基线增加的百分比为 7.14%（SE：0.46%），abaloparatide-SC 为 10.86%（SE：0.48%）（治疗差异：-3.72% [95% 置信区间] ：-5.01%，-2.43%]）。abaloparatide-sMTS 的总髋部 BMD 变化百分比为 1.97%，abaloparatide-SC 的变化百分比为 3.70%。12 个月时血清 I 型前胶原 N 末端前肽 (s-PINP) 相对于基线的中位变化对于 abaloparatide-sMTS 为 52.6%，对于 abaloparatide-SC 为 74.5%。给药部位反应是最常报告的不良事件（abaloparatide-sMTS，94.4%；abaloparatide-SC，70.5%）。各组之间严重不良事件的发生率相似。使用 abaloparatide-sMTS 发生轻度或中度皮肤反应，没有可识别的致敏反应危险因素。两组均很少发生新的临床骨折。未证明 abaloparatide-sMTS 在 12 个月时脊柱 BMD 变化百分比方面不劣于 abaloparatide-SC；然而，在两个治疗组中都观察到腰椎和总髋部 BMD 较基线有临床意义的增加。© 2023 Radius Health, Inc 和作者。《Journal of Bone and Mineral Research》由 Wiley periodicals LLC 代表美国骨与矿物研究学会 (ASBMR) 出版。