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.

中文翻译：

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皮下 tanezumab 治疗髋关节或膝关节骨关节炎：一项为期 24 周的随机 III 期研究的疗效和安全性结果，为期 24 周的随访期

目的在一项为期 24 周的治疗和 24 周的安全性随访研究中，研究了一种神经生长因子抑制剂 Tanezumab 治疗髋关节或膝关节骨关节炎 (OA) 的情况。方法 这项双盲、随机、III 期研究在欧洲和日本招募了对标准镇痛药没有反应或不能耐受的中度至重度 OA 的成年人。患者每 8 周随机接受 tanezumab 2.5 mg 或 5 mg 皮下注射或匹配安慰剂（三剂）。共同主要终点是西安大略和麦克马斯特大学骨关节炎指数 (WOMAC) 疼痛和身体功能以及患者对 OA 的全球评估 (PGA-OA) 从基线到第 24 周的变化。在为期 48 周的研究中继续进行联合安全性和神经系统评估。结果 2016 年 3 月至 2017 年 12 月，849 名患者被随机分配和评估（安慰剂 n=282，tanezumab 2.5 mg n=283，tanezumab 5 mg n=284）。在第 24 周，与安慰剂相比，tanezumab 5 mg 的 WOMAC 疼痛（最小二乘均数差±SE –0.62±0.18，p=0.0006）、WOMAC 身体功能（–0.71±0.17，p< 0.0001) 和 PGA-OA (–0.19±0.07, p=0.0051)。对于 tanezumab 2.5 mg，WOMAC 疼痛和身体功能有统计学意义的改善，但 PGA-OA 没有。在 tanezumab 2.5 mg 和 tanezumab 5 mg 组中，分别有 1.4% (4/283) 和 2.8% (8/284) 的患者观察到快速进展性骨关节炎 (RPOA)，并且没有人接受安慰剂。全关节置换术 (TJRs) 在所有三个治疗组中的分布相似 (6.7%–7.8%)。与安慰剂相比，接受 Tanezumab 治疗的患者出现更多的感觉异常（5 mg）和感觉减退（两种剂量）。结论 Tanezumab 5 mg 在统计学上显着改善了疼痛、身体功能和 PGA-OA，但 tanezumab 2.5 mg 仅达到了两个共同主要终点。与 tanezumab 2.5 mg 相比，tanezumab 5 mg 的 RPOA 发生率更高。TJR 类似地分布在所有三个组中。试用注册号 NCT02709486。