Background Targeted inhibitors of B-cell activating factor (BAFF) have been evaluated in phase III trials in over 4000 patients with systemic lupus erythematosus (SLE). Post hoc analyses of these studies identify greater treatment effect in patients entering with higher disease activity, greater corticosteroid doses, anti double-stranded DNA (dsDNA) and low complement C3 or C4. Objectives To evaluate the efficacy and safety of blisibimod, a BAFF inhibitor, in a population of patients with SLE enriched for high disease activity. Methods 442 patients with SLE with antinuclear antibodies or anti-dsDNA and Safety of Estrogen in Lupus Erythematosus National Assessment – Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥10 on standard-of-care medications were randomised to receive weekly subcutaneous blisibimod (200 mg) or placebo. Corticosteroid taper was encouraged from week 8. The primary end point was the week 52 SLE Responder Index-6 (SRI-6). Results The SRI-6 primary end point was not met. There was a statistically significant steroid-sparing effect, and significantly more blisibimod-treated subjects achieved corticosteroid taper. Increased blisibimod treatment effect on SRI-6 was observed in subjects who achieved a concomitant decrease in corticosteroid dose from baseline. In subjects with baseline urinary protein:creatinine ratio (UPCR) ≥56.5 mg/mmol, significantly higher proportions of blisibimod subjects achieved >50% reduction in UPCR and/or UPCR <56.5 mg/mmol. Reductions in SLE autoantibodies and B cells, and increases in complement C3 and C4 were observed with blisibimod. Blisibimod was well-tolerated. The most common adverse events were upper respiratory tract infection, urinary tract infection, injection site erythema/reaction and diarrhoea. Conclusions Although the SRI-6 end point was not met, blisibimod was associated with successful steroid reduction, decreased proteinuria and biomarker responses. Trial registration number NCT01395745.

中文翻译：

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使用 blisibimod（一种 B 细胞激活因子的选择性抑制剂）治疗系统性红斑狼疮 (SLE) 受试者的 III 期试验结果：随机、双盲、安慰剂对照试验的结果

背景 B 细胞激活因子 (BAFF) 的靶向抑制剂已在 4000 多名系统性红斑狼疮 (SLE) 患者的 III 期试验中进行了评估。对这些研究的事后分析发现，对于疾病活动度更高、皮质类固醇剂量更大、抗双链 DNA (dsDNA) 和补体 C3 或 C4 低的患者，治疗效果更好。目的 评估 BAFF 抑制剂 blisibimod 在疾病活动度高的 SLE 患者群体中的疗效和安全性。方法 442 名具有抗核抗体或抗 dsDNA 和雌激素安全性红斑狼疮国家评估的 SLE 患者 - 系统性红斑狼疮疾病活动指数 (SELENA-SLEDAI) 在标准护理药物上评分 ≥10 随机接受每周皮下注射 blisibimod (200 毫克) 或安慰剂。从第 8 周开始鼓励减少皮质类固醇。主要终点是第 52 周 SLE 反应指数 6 (SRI-6)。结果未达到 SRI-6 主要终点。存在统计学上显着的类固醇保留效应，并且显着更多的 blisibmod 治疗受试者实现了皮质类固醇减量。在皮质类固醇剂量从基线同时减少的受试者中观察到 blisibmod 对 SRI-6 的治疗效果增加。在基线尿蛋白：肌酐比值 (UPCR) ≥ 56 的受试者中。5 mg/mmol，显着更高比例的 blisibimod 受试者在 UPCR 和/或 UPCR <56.5 mg/mmol 中实现了 >50% 的降低。使用 blisibimod 观察到 SLE 自身抗体和 B 细胞的减少，以及补体 C3 和 C4 的增加。Blisibimod 的耐受性良好。最常见的不良事件是上呼吸道感染、尿路感染、注射部位红斑/反应和腹泻。结论 尽管未达到 SRI-6 终点，但 blisibmod 与成功减少类固醇、减少蛋白尿和生物标志物反应相关。试验注册号 NCT01395745。使用 blisibmod 观察到补体 C3 和 C4 增加。Blisibimod 的耐受性良好。最常见的不良事件是上呼吸道感染、尿路感染、注射部位红斑/反应和腹泻。结论 尽管未达到 SRI-6 终点，但 blisibmod 与成功减少类固醇、减少蛋白尿和生物标志物反应相关。试验注册号 NCT01395745。使用 blisibmod 观察到补体 C3 和 C4 增加。Blisibimod 的耐受性良好。最常见的不良事件是上呼吸道感染、尿路感染、注射部位红斑/反应和腹泻。结论 尽管未达到 SRI-6 终点，但 blisibmod 与成功减少类固醇、减少蛋白尿和生物标志物反应相关。试验注册号 NCT01395745。