University College Hospital to University College London, London, UK.
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ann Rheum Dis. 2016 Feb;75(2):323-31. doi: 10.1136/annrheumdis-2015-207653. Epub 2015 Sep 3.
Evaluate efficacy and safety of tabalumab, a human IgG4 monoclonal antibody that binds and neutralises membrane and soluble B-cell activating factor (BAFF) versus placebo plus standard of care (SoC) in patients with systemic lupus erythematosus (SLE).
This phase III, 52-week study randomised 1164 patients with moderate-to-severe SLE (Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index ≥6 at baseline). Patients received SoC plus subcutaneous injections of tabalumab or placebo, starting with a loading dose (240 mg) at week 0 and followed by 120 mg every two weeks (120 Q2W, n=387), 120 mg every four weeks (120 Q4W, n=389) or placebo Q2W (n=388).
proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52.
Similar proportions of patients in each group achieved SRI-5 response at week 52 (120 Q2W: 31.8%; 120 Q4W: 35.2% and placebo: 29.3%). Key secondary endpoints were not met. In a sensitivity analysis not excluding patients who decreased antimalarials or immunosuppressants, SRI-5 response was achieved with 120 Q4W (37.0% vs 29.8% placebo; p=0.021), but not 120 Q2W (34.1%; p=0.171). Significant reductions in anti-dsDNA antibodies, increases in C3 and C4, and reductions in total B cells and immunoglobulins were observed with tabalumab. No differences were observed between treatment groups in percentage of deaths (120 Q2W: 0.8%; 120 Q4W: 0.5%; placebo: 0.5%), serious adverse events (AEs) (range 11.1-14.4%) or treatment-emergent AEs (range 81.1-82.3%).
Tabalumab had biological activity-changes in anti-dsDNA, complement, B cells and immunoglobulins-consistent with BAFF pathway inhibition. Key clinical efficacy endpoints did not achieve statistical significance. Safety profiles were similar with tabalumab and placebo.
NCT01196091.
评估 tabalumab（一种与人 IgG4 单克隆抗体结合并中和膜和可溶性 B 细胞激活因子（BAFF）的药物）与安慰剂加标准治疗（SoC）相比，在中度至重度系统性红斑狼疮（SLE）患者中的疗效和安全性。
这是一项为期 52 周的 III 期研究，共纳入了 1164 名 SLE 患者（安全性雌激素在狼疮红斑评估-SLE 疾病活动指数≥6 基线）。患者接受 SoC 加皮下注射 tabalumab 或安慰剂，起始剂量为 240mg（第 0 周），随后每两周 120mg（120 Q2W，n=387），每四周 120mg（120 Q4W，n=389）或安慰剂 Q2W（n=388）。
第 52 周时达到系统性红斑狼疮应答指数 5（SRI-5）应答的患者比例。
每组达到 SRI-5 应答的患者比例相似（120 Q2W：31.8%；120 Q4W：35.2%和安慰剂：29.3%）。主要次要终点未达到。在不排除减少抗疟药或免疫抑制剂的患者的敏感性分析中，120 Q4W 组达到 SRI-5 应答（37.0%vs安慰剂 29.8%；p=0.021），但 120 Q2W 组未达到（34.1%；p=0.171）。Tabalumab 可显著降低抗 dsDNA 抗体，增加 C3 和 C4，减少总 B 细胞和免疫球蛋白。各组间死亡率（120 Q2W：0.8%；120 Q4W：0.5%；安慰剂：0.5%）、严重不良事件（AEs）（范围 11.1-14.4%）或治疗后 AEs（范围 81.1-82.3%）百分比无差异。
Tabalumab 具有生物学活性——改变抗 dsDNA、补体、B 细胞和免疫球蛋白，与 BAFF 途径抑制一致。主要临床疗效终点未达到统计学意义。Tabalumab 和安慰剂的安全性相似。
NCT01196091。
