Division of Immunology and Rheumatology, Stanford University Medical Center, , Palo Alto, California 94304, USA.
Ann Rheum Dis. 2013 Sep 1;72(9):1453-60. doi: 10.1136/annrheumdis-2012-202864. Epub 2013 Apr 18.
To assess the dose-response relationship, efficacy and safety of tabalumab, a human monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with rheumatoid arthritis (RA) with inadequate response to methotrexate (MTX).
In this phase 2, 24-week, double-blind, placebo-controlled, dose-ranging study, patients with RA (N=158) on stable MTX were randomised by Bayesian-adaptive method to receive 1, 3, 10, 30, 60, or 120 mg tabalumab or placebo subcutaneously every 4 weeks for 24 weeks. The primary objective was to test for a significant dose-response relationship using a statistical model of the proportion of patients having ≥50% improvement in American College of Rheumatology (ACR) criteria (ACR50) at week 24 (prespecified α=0.10).
At week 24, a significant dose-response relationship was observed using ACR50 (p=0.059) and ACR20 (p=0.044) response rates. Using model-estimated data, only 120 mg had significantly higher ACR50 and ACR20 response rates versus placebo (p<0.05). Observed response rates were significantly higher for 120 mg versus placebo as measured by ACR50 at weeks 12 (p=0.039) and 20 (p=0.018), but not week 24, and by ACR20 at weeks 12 (p=0.011) and 24 (p=0.039). Mean DAS28 C-reactive protein improved with 120 mg at week 24 (p=0.048). Frequency of TEAEs was similar across groups (range 50-69%, p=0.884). Ten (8.2%) tabalumab and 5 (13.9%) placebo patients reported a serious adverse event (SAE). Infections occurred more frequently in patients exposed to tabalumab (30.3% vs 19.4%). Serious infections were reported in 3 (2.5%) tabalumab-treated patients only.
A dose-response relationship was detected with monthly subcutaneous tabalumab. A significant effect was detected with the 120 mg dose with no unexpected safety signals. CLINICAL TRIAL #: NCT00785928.
评估 tabalumab（一种中和膜结合和可溶性 B 细胞激活因子（BAFF）的人源单克隆抗体）在对甲氨蝶呤（MTX）反应不足的类风湿关节炎（RA）患者中的剂量 - 反应关系、疗效和安全性。
在这项为期 24 周的、双盲、安慰剂对照、剂量范围研究中，158 例接受 MTX 稳定治疗的 RA 患者按贝叶斯自适应方法随机接受 1、3、10、30、60 或 120 mg tabalumab 或安慰剂皮下注射，每 4 周一次，共 24 周。主要目的是使用 24 周时达到美国风湿病学会（ACR）标准≥50%改善的患者比例（ACR50）的统计模型检验显著的剂量 - 反应关系（预设 α=0.10）。
在第 24 周时，使用 ACR50（p=0.059）和 ACR20（p=0.044）反应率观察到显著的剂量 - 反应关系。使用模型估计数据，仅 120mg 与安慰剂相比具有更高的 ACR50 和 ACR20 反应率（p<0.05）。在第 12 周（p=0.039）和第 20 周（p=0.018），120mg 与安慰剂相比，通过 ACR50 观察到的反应率显著更高，而在第 24 周（p=0.039），通过 ACR20 观察到的反应率也显著更高，在第 24 周（p=0.039），通过 ACR20 观察到的反应率也显著更高。在第 24 周时，120mg 可改善 DAS28 C 反应蛋白（p=0.048）。各组的不良事件（TEAE）发生率相似（范围为 50-69%，p=0.884）。10 名（8.2%）tabalumab 患者和 5 名（13.9%）安慰剂患者报告了严重不良事件（SAE）。暴露于 tabalumab 的患者中感染更为常见（30.3% vs 19.4%）。仅 3 名（2.5%）tabalumab 治疗患者报告了严重感染。
每月皮下注射 tabalumab 可检测到剂量 - 反应关系。在 120mg 剂量时检测到显著效果，无意外安全性信号。临床试验编号：NCT00785928。
