皮下注射塔巴鲁单抗治疗系统性红斑狼疮的疗效和安全性：ILLUMINATE-1 研究 52 周结果，一项多中心、随机、双盲、安慰剂对照的 III 期临床研究。
Efficacy and safety of subcutaneous tabalumab in patients with systemic lupus erythematosus: results from ILLUMINATE-1, a 52-week, phase III, multicentre, randomised, double-blind, placebo-controlled study.
机构信息
University College Hospital to University College London, London, UK.
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
出版信息
Ann Rheum Dis. 2016 Feb;75(2):323-31. doi: 10.1136/annrheumdis-2015-207653. Epub 2015 Sep 3.
OBJECTIVES
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).
METHODS
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).
PRIMARY ENDPOINT
proportion of patients achieving SLE Responder Index 5 (SRI-5) response at week 52.
RESULTS
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%).
CONCLUSIONS
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.
TRIAL REGISTRATION NUMBER
NCT01196091.
目的
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。
方法
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）。
主要终点
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。
结果
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。
结论
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。
试验注册编号
NCT01196091。
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