Division of Immunology and Rheumatology, Stanford University, , Palo Alto, CA 94304, USA.
Ann Rheum Dis. 2013 Sep 1;72(9):1461-8. doi: 10.1136/annrheumdis-2012-202775. Epub 2012 Dec 25.
To evaluate the efficacy and safety of tabalumab, a monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with active rheumatoid arthritis (RA) who showed inadequate response to tumour necrosis factor (TNF) inhibitors.
Patients on stable methotrexate and with inadequate response to one or more TNF inhibitors were randomised to placebo (n=35), 30 mg tabalumab (n=35) or 80 mg tabalumab (n=30) given intravenously at 0, 3 and 6 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology 50% response (ACR50) at week 16 (all tabalumab-treated patients vs placebo).
At week 16, no significant differences were observed in the combined tabalumab group versus placebo in ACR50 (12.7% vs 2.9%, p=0.101) or ACR20 response rates (27.0% vs 17.1%, p=0.198). However, significant differences between the combined tabalumab group and placebo were observed at earlier time points for ACR20, ACR50 and Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) reduction. Treatment-emergent adverse events (AEs) were similar with 30 mg tabalumab (65.7%), 80 mg tabalumab (76.7%) and placebo (71.4%), although certain events occurred more often with tabalumab than placebo (eg, infection, anaemia and gastrointestinal events). Serious AEs occurred in two (6.7%) patients receiving 80 mg tabalumab and three (8.6%) receiving placebo, with one serious infection in the placebo group. Initial increases in total and mature B cells were followed by progressive decreases, despite declines in serum tabalumab.
At week 16, the primary end point was not achieved, but an indication of efficacy was observed at earlier time points. Safety findings for tabalumab were consistent with other biological RA therapies.
NCT00689728.
评估单克隆抗体 tabalumab 的疗效和安全性，该抗体能中和细胞膜结合型和可溶性 B 细胞激活因子（BAFF），用于治疗肿瘤坏死因子（TNF）抑制剂治疗应答不足的活动期类风湿关节炎（RA）患者。
正在接受稳定剂量甲氨蝶呤治疗且对一种或多种 TNF 抑制剂应答不足的患者，被随机分配至安慰剂（n=35）、30mg tabalumab（n=35）或 80mg tabalumab（n=30）组，静脉输注，分别在 0、3 和 6 周给药。主要终点为第 16 周时达到美国风湿病学会 50%应答（ACR50）的患者比例（所有接受 tabalumab 治疗的患者 vs 安慰剂）。
第 16 周时，联合 tabalumab 组与安慰剂组相比，ACR50 应答率（12.7% vs 2.9%，p=0.101）或 ACR20 应答率（27.0% vs 17.1%，p=0.198）均无显著差异。然而，在更早的时间点，联合 tabalumab 组与安慰剂组相比，ACR20、ACR50 和 28 关节疾病活动度评分（DAS28）-C 反应蛋白（CRP）降低均有显著差异。30mg tabalumab（65.7%）、80mg tabalumab（76.7%）和安慰剂（71.4%）的治疗出现的不良事件（AE）相似，但 tabalumab 组比安慰剂组更常发生某些事件（如感染、贫血和胃肠道事件）。80mg tabalumab 组有 2 例（6.7%）和安慰剂组有 3 例（8.6%）患者发生严重 AE，安慰剂组有 1 例严重感染。尽管血清 tabalumab 下降，但总 B 细胞和成熟 B 细胞最初增加后，均逐渐下降。
第 16 周时，主要终点未达到，但在更早的时间点观察到了疗效的迹象。tabalumab 的安全性发现与其他生物 RA 疗法一致。
NCT00689728。
