Insights from the BLISS-LN Phase 3 study of biomarker associations with kidney response to belimumab in lupus nephritis.

Methods

BLISS-LN was a Phase 3 study (NCT01639339) of adults with active LN randomized to intravenous belimumab 10 mg/kg or placebo plus standard therapy (cyclophosphamide [CYC] or mycophenolate mofetil [MMF] as initial therapy followed by azathioprine or MMF).

BLISS-LN是一项III期研究（NCT01639339），纳入了活动性狼疮性肾炎的成年患者，随机接受静脉注射贝利木单抗10 mg/kg或安慰剂加标准治疗（初始治疗为环磷酰胺[CYC]或吗替麦考酚酯[MMF]，随后使用硫唑嘌呤或吗替麦考酚酯[MMF]）。

Absolute and percentage changes from baseline in immunoglobulins, anti-dsDNA and anti-C1q antibodies, C3 and C4, CD19+ B cells and subsets were assessed through Week 104.

通过第104周评估了基线免疫球蛋白、抗dsDNA和抗C1q抗体、C3和C4、CD19+ B细胞及其亚群的绝对值和百分比变化。

Post hoc logistic regression models assessed the association of baseline biomarker levels, and of early changes in biomarkers, with kidney response to belimumab in the overall population at Week 104.

事后逻辑回归模型评估了基线生物标志物水平以及生物标志物早期变化与第104周贝利木单抗对肾脏反应的关联性，针对整体人群。

Results

Of 446 patients (belimumab: 59 received CYC, 164 received MMF; placebo: 59 received CYC, 164 received MMF), approximately 50-60% had data on treatment at Week 104.

在446名患者中（贝利木单抗组：59人接受环磷酰胺，164人接受吗替麦考酚酯；安慰剂组：59人接受环磷酰胺，164人接受吗替麦考酚酯），约50-60%的患者在第104周有治疗数据。

At Week 104, numerically greater percentage reductions in IgA, IgM and anti-dsDNA antibodies and plasmablasts, and greater increases in C3 and C4 levels, were observed with belimumab versus placebo.

在第104周，与安慰剂相比，贝利木单抗组观察到IgA、IgM和抗双链DNA抗体以及浆细胞样细胞的百分比减少数值更大，以及C3和C4水平的增加数值更大。

Overall, belimumab reduced total CD19+ B cells and naïve B cells versus placebo.

总体而言，贝利木单抗相比安慰剂减少了总CD19+ B细胞和初始B细胞的数量。

These results were generally consistent in the overall population and within each induction group.

这些结果在整体人群以及每个诱导组内大致一致。

Predictors of kidney response observed in belimumab-treated patients included high baseline levels of IgA, anti-C1q antibodies and naïve B cells, low baseline plasmablasts and early decreases from baseline in levels of IgA, IgM and urinary protein to creatinine ratio.

观察到接受贝利木单抗治疗的患者肾脏反应的预测因素包括高基线水平的IgA、抗C1q抗体和原始B细胞，以及基线时浆细胞减少和IgA、IgM以及尿蛋白与肌酐比值从基线早期下降。

Conclusions

Similar effects of belimumab on biomarker outcomes were observed within the induction groups.

在诱导组内观察到贝利木单抗对生物标志物结果的类似影响。

Baseline biomarkers and early changes in biomarkers associated with kidney response to belimumab in LN were identified.

识别了与狼疮性肾炎患者肾脏对贝利木单抗反应相关的基线生物标志物和生物标志物的早期变化。