North Shore-Long Island Jewish Health System, Great Neck, New York, USA.
Rheumatology Gynecology & Reproduction Institute, Lima, Peru.
Ann Rheum Dis. 2015 Sep;74(9):1667-75. doi: 10.1136/annrheumdis-2013-205144. Epub 2014 Apr 19.
To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial.
547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI).
Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo.
This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3.
NCT01162681.
评估皮下注射 B 细胞激活因子抑制剂 blisibimod 在系统性红斑狼疮（SLE）患者中的疗效和安全性，该研究为一项剂量范围的 2b 期临床试验。
547 例 SLE 患者，基线时具有抗双链 DNA 或抗核抗体，安全性评估的雌激素在红斑狼疮中的应用-狼疮疾病活动指数（SELENA-SLEDAI）评分≥6，随机接受安慰剂或 blisibimod 三种剂量水平中的一种。主要终点是在第 24 周测量的 SLE 反应指数-5（SRI-5，符合既定 SRI 标准，但 SELENA-SLEDAI 评分改善≥5 分）。
与安慰剂相比，在汇总的 blisibimod 组中，SRI-5 反应率并未显著提高，但与安慰剂相比，在接受最高剂量（每周一次 200mg，QW）blisibimod 治疗的患者中，从第 16 周至第 24 周，SRI 反应率更高，在第 20 周达到统计学意义（p=0.02）。与安慰剂相比，在达到 SELENA-SLEDAI 改善≥8 的患者中，以及在疾病严重程度（SELENA-SLEDAI≥10 且基线时接受皮质类固醇）的亚组患者中，SRI 反应率仍然更高。在基线时蛋白尿比值为 1-6 的患者中，观察到蛋白尿显著减少。与安慰剂相比，抗双链 DNA 抗体、补体 C3 和 C4 显著（p<0.01）变化，B 细胞减少。与安慰剂相比，blisibimod 组未出现严重不良事件或感染（4/280 和 3/266）、死亡（4/280 和 3/266）和恶性肿瘤（2/280 和 2/266）的不平衡。
这项研究成功地确定了一个安全、有效和方便的剂量、研究人群和终点，用于评估 blisibimod 在 3 期的疗效。
NCT01162681。
