Regeneron Pharmaceuticals, Inc., Tarrytown, New York.
Altoona Center for Clinical Research, Duncansville, Pennsylvania.
Arthritis Rheumatol. 2019 Nov;71(11):1824-1834. doi: 10.1002/art.41012. Epub 2019 Sep 20.
To prospectively assess the efficacy, general safety, and joint safety of fasinumab, an anti-nerve growth factor monoclonal antibody, in osteoarthritis (OA) hip and/or knee pain.
Patients with moderate-to-severe OA pain (knee or hip) and history of inadequate response or intolerance to analgesics were randomized to receive fasinumab (at 1 mg, 3 mg, 6 mg, or 9 mg) or placebo every 4 weeks over 16 weeks and were followed up to week 36. Efficacy end points were the change from baseline to week 16 in the pain and physical function subscale scores of the Western Ontario and McMaster Universities OA Index (WOMAC), and patient global assessment (PGA) of OA. Joints were monitored at scheduled assessments (by plain film radiography and magnetic resonance imaging) during treatment and follow-up, and if prompted, at the time of active joint symptoms.
Of the 421 patients randomized, 342 completed the 36-week study. All doses of fasinumab yielded statistically significant and clinically important reductions in pain compared to placebo (least squares mean difference in WOMAC pain subscale scores at week 16 ranging -0.78 to -1.40), without any clear dose dependence. Physical function and PGA scores improved in parallel. Treatment-emergent adverse event rates were 17% with fasinumab and 10% with placebo, and 4% and 1% of patients, respectively, discontinued treatment. Arthropathies (25 in total, 7% of fasinumab-treated patients and 1% of placebo-treated patients) occurred in a dose-dependent manner, with 2 occurring in patients receiving the lowest dose of fasinumab and 10 in patients receiving the highest dose. Most of the arthropathies (16 of 25) were discovered with scheduled radiographs and not based on symptoms. Destructive arthropathy (in 1 of 337 treated patients) occurred in 1 patient who was receiving 6 mg fasimumab.
Fasinumab provided improvements in OA pain and function, even in those benefitting little from previous analgesics. The observed benefit-to-risk relationship favors further clinical development to explore the lowest doses of fasinumab in patients with knee or hip OA.
前瞻性评估 Fasinuumab（一种抗神经生长因子单克隆抗体）在骨关节炎（OA）髋和/或膝关节疼痛中的疗效、总体安全性和关节安全性。
中重度 OA 疼痛（膝关节或髋关节）且既往镇痛药治疗反应不足或不耐受的患者随机接受 Fasinuumab（1mg、3mg、6mg 或 9mg）或安慰剂，每 4 周一次，共 16 周，并随访至 36 周。疗效终点为 Western Ontario 和 McMaster 大学骨关节炎指数（WOMAC）疼痛和身体功能子量表评分以及 OA 患者总体评估（PGA）从基线到第 16 周的变化。在治疗和随访期间，根据预定评估（通过普通 X 线摄影和磁共振成像）以及在出现活跃关节症状时监测关节，如果有必要。
在 421 名随机患者中，342 名完成了 36 周的研究。与安慰剂相比，所有剂量的 Fasinuumab 均能显著降低疼痛（第 16 周 WOMAC 疼痛子量表评分的最小二乘均值差异为-0.78 至-1.40），且无明显的剂量依赖性。身体功能和 PGA 评分均有改善。 Fasinuumab 的治疗中出现的不良事件发生率为 17%，安慰剂为 10%，分别有 4%和 1%的患者停止治疗。关节病（总共 25 例，Fasinuumab 治疗患者的 7%和安慰剂治疗患者的 1%）呈剂量依赖性，2 例发生在接受最低剂量 Fasinuumab 的患者中，10 例发生在接受最高剂量的患者中。大多数关节病（25 例中的 16 例）是通过常规 X 线片发现的，而不是基于症状。破坏性关节炎（在 337 名治疗患者中的 1 名）发生在接受 6mg Fasimumab 的 1 名患者中。
Fasinuumab 改善了 OA 的疼痛和功能，即使是那些对以前的镇痛药受益不大的患者。观察到的获益与风险关系有利于进一步的临床开发，以探索膝或髋 OA 患者中最低剂量的 Fasinuumab。
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