ObjectiveA phase II trial tested different doses of the anti‐CD40 monoclonal antibody BI655064 as add‐on therapy to the standard of care in class III or IV Lupus Nephritis (LN) patients with active disease. A post‐hoc analysis showed a potential benefit of the higher tested doses (180mg/240mg) versus low dose (120mg)/placebo. We investigated whether the treatment effect of BI655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well‐known role in LN pathogenesis.Methods101 renal biopsies of LN patients enrolled in the BI655064 trial were scored centrally. eGFR and spot urine protein/urine creatinine ratio (UP/UC) and Complete Renal Response (CRR) were evaluated over 52 weeks. Patients were divided according to a “Better” or “Worse” performance than the average of all patients in the cohort, predicted by a mixed model for repeated measurements. Logistic regression models adjusted for potential confounders assessed the association between different treatment doses and outcomes according to the presence or absence of monocytes.ResultsA higher BI655064 dose (180/240mg) was associated with better outcomes of UP/UC and CRR when glomerular monocytes were present in kidney biopsies (OR 3.66[1.09‐12.3], P=0.04; OR 4.58[1.24‐16.9], P=0.02). A trend toward improved eGFR was also observed in these patients (P 52‐weeks=0.08).ConclusionsIn LN kidney biopsies with glomerular monocytes, high‐dose BI655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsies without glomerular monocytes. Histologic features may guide the choice of treatment for individual LN patients.

中文翻译：

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根据肾活检特征接受抗 CD40 单克隆抗体治疗的狼疮性肾炎患者的结局


目的一项 II 期试验测试了不同剂量的抗 CD40 单克隆抗体BI655064作为 III 类或 IV 类狼疮肾炎 （LN） 活动性疾病患者护理标准的附加疗法。一项事后分析显示，与低剂量 （120mg）/安慰剂相比，较高测试剂量 （180mg/240mg） 具有潜在益处。我们研究了 BI655064 对肾脏结局的治疗效果是否可以通过肾小球单核细胞的存在而改变，肾小球单核细胞是该药物的靶点，在 LN 发病机制中具有众所周知的作用。方法对 BI655064 试验中入组的 101 例 LN 患者肾活检进行集中评分。在 52 周内评估 eGFR 和随机尿蛋白/尿肌酐比值 （UP/UC） 和完全肾反应 （CRR）。根据比队列中所有患者平均值的“更好”或“更差”表现对患者进行划分，由重复测量的混合模型预测。针对潜在混杂因素进行调整的 Logistic 回归模型根据单核细胞的存在与否评估不同治疗剂量和结果之间的关联。结果当肾小球活检中存在肾小球单核细胞时，较高的 BI655064 剂量 （180/240mg） 与 UP/UC 和 CRR 的更好结局相关 （OR 3.66[1.09‐12.3]，P=0.04;或 4.58[1.24‐16.9]，P=0.02）。在这些患者中也观察到 eGFR 改善的趋势 （P 52 周 = 0.08）。结论在肾小球单核细胞的 LN 肾活检中，与无肾小球单核细胞的活检相比，高剂量 BI655064 治疗改善了 52 周时的蛋白尿，并导致更高的 CRR。组织学特征可指导个体 LN 患者的治疗选择。