Experimental Medicine Unit, GlaxoSmithKline R&D, UK.
Renal Unit, Addenbrooke's Hospital, UK.
Nephrol Dial Transplant. 2020 Apr 1;35(4):599-606. doi: 10.1093/ndt/gfz086.
Immunosuppressant drugs reduce proteinuria and anti-phospholipase A2 receptor autoantibodies (PLA2R-Ab) in primary membranous nephropathy (PMN) with varying success and associated toxicities. This study aimed to evaluate the effect of belimumab on proteinuria and PLA2R-Ab in participants with PMN.
In this prospective, open-label, experimental medicine study, 14 participants with PMN and persistent nephrotic-range proteinuria received up to 2 years belimumab monotherapy (10 mg/kg, every 4 weeks). Changes in proteinuria (urinary protein:creatinine ratio), PLA2R-Ab, albumin, cholesterol, B-cell subsets and pharmacokinetics were analysed during treatment and up to 6 months after treatment.
Eleven participants completed to the primary endpoint (Week 28) and nine participants completed the study. In the intention-to-treat population population, baseline proteinuria of 724 mg/mmol [95% confidence interval (CI) 579-906] decreased to 498 mg/mmol (95% CI 383-649) and 130 mg/mmol (95% CI 54-312) at Weeks 28 and 104, respectively, with changes statistically significant from Week 36 (n = 11, P = 0.047). PLA2R-Ab decreased from 174 RU/mL (95% CI 79-384) at baseline to 46 RU/mL (95% CI 16-132) and 4 RU/mL (95% CI 2-6) at Weeks 28 and 104, respectively, becoming statistically significant by Week 12 (n = 13, P = 0.02). Nine participants achieved partial (n = 8) or complete (n = 1) remission. Participants with abnormal albumin and/or cholesterol at baseline gained normal/near normal levels by the last follow-up. Adverse events were consistent with those expected in this population.
Belimumab treatment in participants with PMN can reduce PLA2R-Ab and subsequently proteinuria, important preludes to remission induction.
免疫抑制剂可降低原发性膜性肾病（PMN）患者的蛋白尿和抗磷脂酶 A2 受体自身抗体（PLA2R-Ab），但疗效和相关毒性不一。本研究旨在评估贝利尤单抗对PMN 患者蛋白尿和 PLA2R-Ab 的影响。
在这项前瞻性、开放标签、实验医学研究中，14 名PMN 患者且持续存在肾病范围蛋白尿，接受了长达 2 年的贝利尤单抗单药治疗（10mg/kg，每 4 周 1 次）。在治疗期间和治疗结束后 6 个月内，分析了蛋白尿（尿蛋白：肌酐比值）、PLA2R-Ab、白蛋白、胆固醇、B 细胞亚群和药代动力学的变化。
11 名患者完成了主要终点（第 28 周），9 名患者完成了研究。在意向治疗人群中，基线蛋白尿 724mg/mmol [95%置信区间（CI）579-906] 降至第 28 周和第 104 周的 498mg/mmol（95%CI 383-649）和 130mg/mmol（95%CI 54-312），第 36 周时（n=11，P=0.047）有统计学意义。PLA2R-Ab 从基线时的 174RU/mL（95%CI 79-384）降至第 28 周和第 104 周的 46RU/mL（95%CI 16-132）和 4RU/mL（95%CI 2-6），第 12 周（n=13，P=0.02）时具有统计学意义。9 名患者获得部分（n=8）或完全（n=1）缓解。基线白蛋白和/或胆固醇异常的患者在最后一次随访时恢复正常/接近正常水平。不良事件与该人群预期的一致。
贝利尤单抗治疗PMN 患者可降低 PLA2R-Ab，随后降低蛋白尿，这是诱导缓解的重要前提。
