DiMartino Stephen J, Mei Jingning, Schnitzer Thomas J, Gao Haitao, Eng Simon, Winslow Christine, Ho Tina, Turner Kenneth C, Hassan Hazem E, Patel Yamini, Davis John D, Trinh Ngan, Manley Angela, Manvelian Garen, Fetell Michael, Braunstein Ned, Geba Gregory P, Dakin Paula
Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Osteoarthr Cartil Open. 2024 Oct 22;6(4):100533. doi: 10.1016/j.ocarto.2024.100533. eCollection 2024 Dec.
Pain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain.
In this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 mg every 4 weeks [Q4W] and 1 and 6 mg every 8 weeks [Q8W] for 52 weeks). Primary safety endpoints included adverse events, adjudicated arthropathies (AAs), and joint replacements (JRs). Co-primary endpoints of an efficacy sub-study were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores. During the study, higher fasinumab doses were discontinued for safety; 1 mg doses continued.
Of 13,945 patients screened, 5331 were randomized; 1074 were included in the efficacy sub-study. AAs and JRs occurred in all groups. Increased severity of disease at baseline was associated with higher rates of AAs and JRs. A dose-dependent risk of AA or JR was observed for fasinumab; in the 1 mg groups, only a small percentage of patients with JR had prior AA. Fasinumab significantly improved WOMAC pain and physical function scores compared with placebo; least squares mean differences versus placebo were -1.22 and -1.20 for 1 mg Q4W and -0.73 and -0.74 for 1 mg Q8W, respectively (0.001).
AAs and JRs showed a dose relationship to fasinumab and were associated with baseline OA status. Fasinumab achieved statistically significant improvements in WOMAC pain and physical function scores compared with placebo.
骨关节炎（OA）相关疼痛常常使人致残；治疗方法往往无效或难以耐受。法西珠单抗可选择性抑制神经生长因子，已显示出对OA疼痛的治疗效果。
在这项随机、双盲、III期安全性研究中，有中度至重度OA疼痛且疼痛缓解不足病史的患者接受安慰剂或法西珠单抗治疗（每4周1、3、6和9毫克[Q4W]，以及每8周1和6毫克[Q8W]，持续52周）。主要安全性终点包括不良事件、经判定的关节病（AA）和关节置换（JR）。疗效亚研究的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）疼痛和身体功能评分的变化。在研究期间，因安全性原因停用了较高剂量的法西珠单抗；1毫克剂量继续使用。
在13945名筛查患者中，5331名被随机分组；1074名被纳入疗效亚研究。所有组均出现了AA和JR。基线时疾病严重程度增加与AA和JR的发生率较高相关。观察到法西珠单抗存在AA或JR的剂量依赖性风险；在1毫克组中，只有一小部分接受JR的患者曾有过AA。与安慰剂相比，法西珠单抗显著改善了WOMAC疼痛和身体功能评分；1毫克Q4W与安慰剂相比最小二乘均值差异分别为-1.22和-1.20，1毫克Q8W与安慰剂相比最小二乘均值差异分别为-0.73和-0.74（P<0.001）。
AA和JR与法西珠单抗呈剂量关系，并与基线OA状态相关。与安慰剂相比，法西珠单抗在WOMAC疼痛和身体功能评分方面取得了具有统计学意义的改善。
