Su Xiaole, Wu Binxin, Tie Xuan, Guo Xiaojiao, Feng Rongrong, Qiao Xi, Wang Lihua
Department of Nephrology, Second Hospital of Shanxi Medical University, Taiyuan, China.
Shanxi Kidney Disease Institute, Taiyuan, China.
Kidney Int Rep. 2024 May 13;9(8):2386-2398. doi: 10.1016/j.ekir.2024.05.004. eCollection 2024 Aug.
B-cell lymphocytes have been demonstrated to play a key role in the pathogenesis underlying membranous nephropathy (MN). The aim of this study was to evaluate the therapeutic efficacy and safety of Obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody in individuals with MN.
We retrospectively analyzed data from 59 consecutive patients with primary MN who provided consent to receive Obinutuzumab and were followed for at least 6 months. The primary outcomes were complete (proteinuria <0.3 g/d) or partial (proteinuria <3.5 g/d with ≥ 50% reduction) remission of proteinuria.
Twenty patients received Obinutuzumab as initial therapy, and 39 patients were previously treated with at least 1 immunosuppressant (second-line therapy). Fifty patients (84.7%) achieved complete remission (CR) or partial remission (PR) of proteinuria during the median follow-up of 9.4 months. The likelihood of remission was significantly higher when Obinutuzumab was used as initial therapy than as second-line therapy after adjusting for the baseline estimated glomerular filtration rate (eGFR), 24-hour urinary protein levels, and anti-phospholipase A receptor (PLAR) status (adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI]: 2.1-9.5, 0.001). Circulating CD19 B-cell count decreased to <5 cells/μl in all patients within 2 weeks after infusion. Serum anti-PLAR concentrations decreased to <14 relative units (RU)/ml in 43 of 48 patients with PLAR-related MN. After Obinutuzumab administration, a significant reduction in 24-hour urine protein and increase in serum albumin were observed. No serious adverse events were observed.
Obinutuzumab may represent a promising and well-tolerated therapeutic option for individuals with primary MN. The potential of Obinutuzumab was highlighted as an initial therapy for primary MN.
已证实B淋巴细胞在膜性肾病（MN）的发病机制中起关键作用。本研究的目的是评估奥妥珠单抗（一种糖基化工程化的II型抗CD20单克隆抗体）对MN患者的治疗效果和安全性。
我们回顾性分析了59例连续的原发性MN患者的数据，这些患者同意接受奥妥珠单抗治疗并至少随访6个月。主要结局是蛋白尿完全缓解（蛋白尿<0.3 g/d）或部分缓解（蛋白尿<3.5 g/d且减少≥50%）。
20例患者接受奥妥珠单抗作为初始治疗，39例患者先前至少接受过1种免疫抑制剂治疗（二线治疗）。在中位随访9.4个月期间，50例患者（84.7%）实现了蛋白尿的完全缓解（CR）或部分缓解（PR）。在调整基线估计肾小球滤过率（eGFR）、24小时尿蛋白水平和抗磷脂酶A受体（PLAR）状态后，奥妥珠单抗作为初始治疗时缓解的可能性显著高于二线治疗（调整后的风险比[HR]，4.5；95%置信区间[CI]：2.1-9.5，P<0.001）。输注后2周内，所有患者的循环CD19 B细胞计数均降至<5个细胞/μl。48例PLAR相关MN患者中有43例血清抗PLAR浓度降至<14相对单位（RU）/ml。给予奥妥珠单抗后，观察到24小时尿蛋白显著减少，血清白蛋白增加。未观察到严重不良事件。
奥妥珠单抗可能是原发性MN患者一种有前景且耐受性良好的治疗选择。奥妥珠单抗作为原发性MN初始治疗的潜力得到了凸显。
