BACKGROUND Children with multidrug-resistant nephrotic syndrome (MRNS) are exposed to drug toxicity (steroids/calcineurin inhibitors (CNI)/mycophenolate mofetil (MMF)) and have an increased risk of kidney disease progression. In small case series, the fully humanized anti-CD20 antibody ofatumumab (OFA) induced remission in children with MRNS when at high dose (10,300 mg/1.73 m2) and partial remission at standard dose (1000 mg/1.73 m2). METHODS This double-blind randomized placebo-controlled trial tested the efficacy of single infusion OFA in children with proven MRNS and initial chronic renal failure (eGFR [median/range] 119/38-155 ml/min/1.73 m2 in Placebo arm vs. 65/19-103 ml/min/1.73 m2 Intervention). Children who had been resistant to a combination of CNI and steroids, with or without MMF or rituximab, were randomized to receive single infusion OFA (1500 mg/1.73 m2) (Intervention arm) or normal saline (Placebo arm). We assessed complete or partial remission of proteinuria after 3 months (primary outcome), and after 6 and 12 months (secondary outcomes), as well as progression to end-stage kidney disease. RESULTS After 13 of the planned 50 children (25%) were randomized, the data safety and monitoring board recommended study termination for futility. All 13 children remained nephrotic. Renal function worsened in 5 children (2 in Intervention arm, 3 in Placebo arm) who required renal replacement therapy during the study period. Circulating CD20 was reduced following OFA infusion and remained low for > 3 months. CONCLUSIONS OFA given in one single infusion of 1500 mg/1.73 m2 doses does not induce remission in MRNS. Regimens based on higher OFA doses should be tested in clinical trials. TRIAL REGISTRATION https://clinicaltrials.gov: NCT02394106.

中文翻译：

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小剂量奥他木单抗用于儿童多药耐药性肾病综合征：一项随机安慰剂对照试验。

背景技术患有多药耐药性肾病综合征（MRNS）的儿童暴露于药物毒性（类固醇/钙调神经磷酸酶抑制剂（CNI）/霉酚酸酯（MMF））并增加了肾脏疾病进展的风险。在小病例系列研究中，高剂量（10,300 mg / 1.73 m2）时，完全人源化的抗CD20抗体ofatumumab（OFA）诱导MRNS儿童缓解，而标准剂量（1000 mg / 1.73 m2）则部分缓解。方法该双盲随机安慰剂对照试验测试了单次输注OFA对已证实具有MRNS和初始慢性肾功能衰竭的儿童的疗效（安慰剂组与对照组相比，eGFR [中位数/范围] 119 / 38-155 ml / min / 1.73 m2）。 65 / 19-103 ml / min / 1.73 m2干预）。对含有或不含MMF或利妥昔单抗的CNI和类固醇联合耐药的儿童，随机接受单次输注OFA（1500 mg / 1.73 m2）（干预组）或生理盐水（安慰剂组）。我们评估了3个月（主要结局），6个月和12个月（继发结局）以及进展为终末期肾脏疾病后蛋白尿的全部或部分缓解。结果在计划的50名儿童中有13名（25％）被随机分配后，数据安全和监控委员会建议终止研究以免徒劳。所有13名儿童仍处于肾病状态。在研究期间需要肾脏替代治疗的5名儿童（干预组2例，安慰剂组3例）的肾功能恶化。OFA输注后循环CD20减少，并且维持低水平> 3个月。结论一次单次1500 mg / 1.73 m2剂量的OFA不会引起MRNS缓解。基于较高OFA剂量的方案应在临床试验中进行测试。试用注册https://clinicaltrials.gov：NCT02394106。