Department of Rheumatology, Sorbonne Université, INSERM CRSA, AP-HP Hopital Saint Antoine, Paris, France
Servicio de Reumatología, INIBC-Complejo Hospitalario Universitario A Coruña, La Coruña, Spain.
Ann Rheum Dis. 2020 Jun;79(6):800-810. doi: 10.1136/annrheumdis-2019-216296. Epub 2020 Mar 31.
OBJECTIVE: Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up. METHODS: This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study. RESULTS: From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo. CONCLUSION: Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups. TRIAL REGISTRATION NUMBER: NCT02709486.
目的：神经生长因子抑制剂替扎尼定用于髋或膝关节骨关节炎的研究中，该研究的治疗期为 24 周，安全性随访期为 24 周。
方法：这项双盲、随机、III 期研究纳入了欧洲和日本的中重度骨关节炎成年患者，这些患者对标准治疗药物的镇痛药无反应或不耐受。患者按 2:2:1 的比例随机接受替扎尼定 2.5mg、5mg 或匹配安慰剂皮下注射，每 8 周（3 剂）一次。主要终点为从基线到第 24 周时的 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）疼痛和躯体功能以及患者总体评估骨关节炎（PGA-OA）的变化。整个 48 周研究期间持续进行关节安全性和神经学评估。
结果：2016 年 3 月至 2017 年 12 月，849 例患者被随机分组并接受评估（安慰剂组 282 例，替扎尼定 2.5mg 组 283 例，替扎尼定 5mg 组 284 例）。第 24 周时，与安慰剂相比，替扎尼定 5mg 组在 WOMAC 疼痛（最小二乘均数差异±SE-0.62±0.18，p=0.0006）、WOMAC 躯体功能（-0.71±0.17，p<0.0001）和 PGA-OA（-0.19±0.07，p=0.0051）方面有统计学意义的改善。替扎尼定 2.5mg 组在 WOMAC 疼痛和躯体功能方面有统计学意义的改善，但在 PGA-OA 方面没有。分别有 1.4%（4/283）和 2.8%（8/284）接受替扎尼定 2.5mg 和替扎尼定 5mg 治疗的患者发生快速进展性骨关节炎（RPOA），而接受安慰剂治疗的患者均未发生。所有三组治疗中全膝关节置换术（TJR）的分布相似（6.7%-7.8%）。与安慰剂相比，替扎尼定治疗患者更常出现感觉异常（5mg）和感觉迟钝（两种剂量）。
结论：替扎尼定 5mg 可显著改善疼痛、躯体功能和 PGA-OA，但替扎尼定 2.5mg 仅达到了两个主要终点。与替扎尼定 2.5mg 相比，替扎尼定 5mg 发生 RPOA 的频率更高。TJR 在三组中的分布相似。
试验注册号：NCT02709486。
Front Vet Sci. 2025-5-9
Curr Pain Headache Rep. 2025-3-18
Pain Manag. 2024-12
Adv Healthc Mater. 2025-1
Nature. 2018-11
Osteoarthritis Cartilage. 2015-1
Osteoarthritis Cartilage. 2015-1
Zotero 插件
