Osteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients. In this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs). A total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of − 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [− 1.34 to 2.11], 0.04 [− 1.61 to 1.69], and 0.41 [− 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs. The efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months. ClinicalTrials.gov, NCT03293108 ; Registration date: 2017–09-19.

中文翻译：

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与参考产品 (Prolia®) 相比，生物仿制药地诺单抗 (Arylia) 在绝经后骨质疏松症中的疗效和安全性：一项 III 期、随机、双臂、双盲、平行、主动对照和非劣效性临床试验

骨质疏松症是一个全球性的健康问题，在全球范围内日益流行。地诺单抗是一种抗吸收剂，已被证明对骨质疏松症患者有效且安全。本研究旨在比较生物仿制药地诺单抗 (Arylia) 与原研产品 (Prolia®) 在绝经后骨质疏松症患者中的疗效和安全性。在这项随机、双盲、主动对照、非劣效性试验中，绝经后骨质疏松症患者在第 0、6 和 12 个月接受 60 mg 皮下注射 Arylia 或 Prolia®，并随访 18 个月。主要终点是生物仿制药产品在 18 个月内腰椎 (L1-L4)、全髋和股骨颈的骨矿物质密度 (BMD) 百分比变化方面的非劣效性。次要终点是安全性评估，新椎体骨折的发生率，以及骨转换标志物（BTMs）的趋势。共有 190 名患者被随机分配接受生物仿制药（n = 95）或参考（n = 95）狄诺塞麦。在符合方案 (PP) 分析中，Arylia 和 Prolia® 在增加 BMD 方面的差异的 95% 双边置信区间的下限大于腰椎、全髋关节的预定非劣效性界值 − 1.78和股骨颈部位（平均差异 [95% CI] 分别为 0.39 [- 1.34 至 2.11]、0.04 [- 1.61 至 1.69] 和 0.41 [- 1.58 至 2.40]）。这两款产品在安全性、新发椎体骨折和 BTM 趋势方面也具有可比性。生物仿制药地诺单抗的疗效不劣于参考地诺单抗，在 18 个月时具有可比的安全性。ClinicalTrials.gov，NCT03293108；注册日期：2017-09-19。