Rheumatology Division , School of Medicine, University of Colorado , Denver , USA.
Department of Rheumatology , Lapeyronie Hospital, Montpellier 1 University , Montpellier , France.
RMD Open. 2015 Aug 12;1(1):e000037. doi: 10.1136/rmdopen-2014-000037. eCollection 2015.
Tabalumab is a human monoclonal antibody that neutralises B-cell activating factor.
To evaluate tabalumab efficacy and safety in patients with rheumatoid arthritis (RA).
This phase 3, randomised, double-blind, placebo-controlled study evaluated 456 patients with active RA after 24-week treatment with subcutaneous tabalumab (120 mg every 4 weeks (120/Q4W) or 90 mg every 2 weeks (90/Q2W)) versus placebo, with loading doses (240 or 180 mg) at week 0. Patients were allowed background disease-modifying antirheumatic drugs and previously discontinued ≥1 tumour necrosis factor α inhibitors for lack of efficacy/intolerance. Primary end point was American College of Rheumatology 20% (ACR20) response at 24 weeks. This study was terminated early due to futility.
Most patients had moderate-to-high baseline disease activity. There was no significant difference in week 24 ACR20 responses between 120/Q4W, 90/Q2W, and placebo (17.6%, 24.3%, 20%) per non-responder imputation analysis. Mean percent changes in CD20+ B-cell count (-10.8%, -9.6%, +10.9%) demonstrated expected pharmacodynamic effects. Treatment-emergent adverse events (AEs) were similar (59.5%, 51.7%, 52.6%), as were AE discontinuations (2.6%, 2.7%, 2.6%), serious AEs (4.6%, 4.1%, 3.9%), serious infectious events (1.3%, 0, 0) and events of interest: infections (23.5%, 25.9%, 24%), injection site reactions (13.1%, 25.8%, 11%) and allergy/hypersensitivity (3.9%, 4.1%, 3.9%) reports. Incidence of treatment-emergent antidrug antibodies was similar to placebo (3.9%, 4.8%, 3.9%). No deaths or new/unexpected safety findings were reported.
Tabalumab did not demonstrate clinical efficacy in patients with RA in this phase 3 study, despite evidence of biological activity. There were no notable differences in safety parameters between tabalumab treatment groups and placebo.
NCT01202773.
Tabalumab 是一种中和 B 细胞激活因子的人源单克隆抗体。
评估 tabalumab 在类风湿关节炎 (RA) 患者中的疗效和安全性。
这是一项 3 期、随机、双盲、安慰剂对照研究，评估了 456 例在接受 24 周皮下注射 tabalumab（120mg 每 4 周（120/Q4W）或 90mg 每 2 周（90/Q2W））或安慰剂治疗后有活动期 RA 的患者，在第 0 周给予负荷剂量（240 或 180mg）。患者允许使用背景疾病修饰抗风湿药物和之前因疗效不佳/不耐受而停用的≥1 种肿瘤坏死因子 α 抑制剂。主要终点为 24 周时美国风湿病学会 20%（ACR20）应答。由于无效，该研究提前终止。
大多数患者基线疾病活动度为中高度。在非应答者推断分析中，120/Q4W、90/Q2W 和安慰剂组在第 24 周时的 ACR20 应答率无显著差异（17.6%、24.3%、20%）。CD20+B 细胞计数的平均百分比变化（-10.8%、-9.6%、+10.9%）表明存在预期的药效学效应。治疗出现的不良事件（AE）相似（59.5%、51.7%、52.6%），AE 停药率相似（2.6%、2.7%、2.6%），严重 AE 发生率相似（4.6%、4.1%、3.9%），严重感染事件发生率相似（1.3%、0、0）和关注事件：感染（23.5%、25.9%、24%）、注射部位反应（13.1%、25.8%、11%）和过敏/超敏反应（3.9%、4.1%、3.9%）报告。治疗出现的抗药物抗体发生率与安慰剂相似（3.9%、4.8%、3.9%）。未报告死亡或新的/意外的安全性发现。
尽管有生物学活性证据，但在这项 3 期研究中，tabalumab 并未显示出 RA 患者的临床疗效。tabalumab 治疗组与安慰剂组在安全性参数方面无显著差异。
NCT01202773。
