Lane Nancy E, Betah Donald, Deignan Cynthia, Oates Mary, Wang Zhenxun, Timoshanko Jen, Khan Aliya A, Binkley Neil
University of California, Davis Health, Sacramento.
Amgen Inc, Thousand Oaks, California.
ACR Open Rheumatol. 2024 Jan;6(1):43-51. doi: 10.1002/acr2.11619. Epub 2023 Nov 20.
Romosozumab is a bone-forming agent approved for osteoporosis treatment. Here we report results of the protocol-specified, noninferiority osteoarthritis substudy of the fracture study in postmenopausal women with osteoporosis (FRAME), which evaluated the effect of romosozumab versus placebo on knee osteoarthritis in patients with a clinical history of osteoarthritis.
Women in FRAME with a history of knee osteoarthritis were eligible for enrollment in the osteoarthritis substudy; key inclusion criteria were osteoarthritis-related signal knee pain, morning stiffness lasting less than 30 minutes, knee crepitus, and knee osteoarthritis confirmed by x-ray within 12 months. The protocol-specified outcomes were change from baseline through month 12 in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, incidence of worsening knee osteoarthritis, and treatment-emergent adverse events (TEAEs) with romosozumab versus placebo. In a post hoc analysis, percentage change from baseline to month 12 in bone mineral density (BMD) was assessed.
Of 7180 women in FRAME, 347 participated in the osteoarthritis substudy (placebo, 177; romosozumab, 170). At month 12, no significant difference in progression of knee osteoarthritis was observed with romosozumab versus placebo (least squares mean total WOMAC score: -2.2 vs. -1.3; P = 0.71). Incidence of worsening symptoms of knee osteoarthritis was comparable between romosozumab (17.1%) and placebo (20.5%) (odds ratio 0.9 [95% confidence interval: 0.5, 1.7]; P = 0.69). Incidence of TEAEs of osteoarthritis was numerically lower with romosozumab (13 [7.7%]) versus placebo (21 [12.0%]). BMD gains were higher with romosozumab.
Romosozumab treatment did not impact knee pain or function in postmenopausal women with osteoporosis and knee osteoarthritis and resulted in significant BMD gains in these women.
罗莫单抗是一种已获批用于治疗骨质疏松症的促骨形成药物。在此，我们报告了骨质疏松症绝经后女性骨折研究（FRAME）中方案指定的骨关节炎非劣效性子研究的结果，该研究评估了罗莫单抗与安慰剂对有骨关节炎临床病史患者的膝关节骨关节炎的影响。
FRAME中具有膝关节骨关节炎病史的女性有资格参加骨关节炎子研究；关键纳入标准为与骨关节炎相关的膝关节信号性疼痛、持续时间少于30分钟的晨僵、膝关节摩擦音以及在12个月内通过X线证实的膝关节骨关节炎。方案指定的结局指标为从基线到第12个月时西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分的变化、膝关节骨关节炎病情恶化的发生率以及罗莫单抗与安慰剂相比的治疗中出现的不良事件（TEAE）。在一项事后分析中，评估了从基线到第12个月骨矿物质密度（BMD）的百分比变化。
在FRAME的7180名女性中，347名参与了骨关节炎子研究（安慰剂组177名；罗莫单抗组170名）。在第12个月时，罗莫单抗与安慰剂相比，膝关节骨关节炎进展无显著差异（最小二乘均数总WOMAC评分：-2.2对-1.3；P = 0.71）。罗莫单抗组（17.1%）和安慰剂组（20.5%）膝关节骨关节炎症状恶化的发生率相当（比值比0.9 [95%置信区间：0.5, 1.7]；P = 0.69）。罗莫单抗组骨关节炎TEAE的发生率在数值上低于安慰剂组（13例[7.7%]对21例[12.0%]）。罗莫单抗组的BMD增加更高。
罗莫单抗治疗对患有骨质疏松症和膝关节骨关节炎的绝经后女性的膝关节疼痛或功能无影响，但这些女性的BMD有显著增加。
