Division of Nephrology, University of Calgary, Calgary, Alberta, Canada.
Renal Diseases Research Unit, Genetics and Rare Diseases Division, Bambino Gesù Children's Hospital Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
J Am Soc Nephrol. 2021 Oct;32(10):2652-2663. doi: 10.1681/ASN.2021040561. Epub 2021 Sep 20.
The chimeric anti-CD20 monoclonal antibody rituximab is effective in steroid-dependent and calcineurin inhibitor-dependent forms of nephrotic syndrome, but many patients relapse at 1 year. Because ofatumumab, a fully human anti-CD20 monoclonal antibody, has a more extended binding site and higher affinity to CD20 compared with rituximab, it might offer superior efficacy in these patients.
We designed a single-center randomized clinical trial to compare the long-term efficacy of ofatumumab versus rituximab in children and young adults with nephrotic syndrome maintained in remission with prednisone and calcineurin inhibitors. We randomized 140 children and young adults (aged 2-24 years) to receive intravenous ofatumumab (1.50 mg/1.73 m) or rituximab (375 mg/m). After infusions, oral drugs were tapered and withdrawn within 60 days. The primary outcome was relapse at 1 year, which was analyzed following the intent-to-treat principle. The secondary endpoint was relapse within 24 months from infusion, on the basis of urine dipstick and confirmed by a urine protein-to-creatinine ratio <200.
At 12 months, 37 of 70 (53%) participants who received ofatumumab experienced relapse versus 36 of 70 (51%) who received rituximab (odds ratio [OR], 1.06; 95% confidence interval [95% CI], 0.55 to 2.06). At 24 months, 53 of 70 (76%) participants who received ofatumumab experienced relapse, versus 46 of 70 (66%) who received rituximab (OR, 1.6; 95% CI, 0.8 to 3.3). The two groups exhibited comparable B cell subpopulation reconstitution and did not differ in adverse events.
A single dose of ofatumumab was not superior to a single dose of rituximab in maintaining remission in children with steroid-dependent and calcineurin inhibitor-dependent nephrotic syndrome.
ClinicalTrials.gov (NCT02394119) and https://www.clinicaltrialsregister.eu/ctr-search/search (2015-000624-28).
嵌合抗 CD20 单克隆抗体利妥昔单抗在激素依赖和钙调磷酸酶抑制剂依赖型肾病综合征中有效，但许多患者在 1 年内复发。由于奥法木单抗是一种完全人源抗 CD20 单克隆抗体，与利妥昔单抗相比，它与 CD20 的结合部位更广泛，亲和力更高，因此在这些患者中可能具有更好的疗效。
我们设计了一项单中心随机临床试验，比较奥法木单抗与利妥昔单抗在维持泼尼松和钙调磷酸酶抑制剂缓解的儿童和年轻成人肾病综合征中的长期疗效。我们将 140 名年龄在 2-24 岁的儿童和年轻成人随机分为静脉注射奥法木单抗（1.50mg/1.73m）或利妥昔单抗（375mg/m）组。输注后，在 60 天内逐渐减少口服药物并停药。主要结局为 1 年时复发，按意向治疗原则进行分析。次要终点为输注后 24 个月内复发，基于尿试纸并通过尿蛋白/肌酐比<200 确认。
在 12 个月时，70 名接受奥法木单抗治疗的参与者中有 37 名（53%）复发，而 70 名接受利妥昔单抗治疗的参与者中有 36 名（51%）复发（比值比[OR]，1.06；95%置信区间[95%CI]，0.55 至 2.06）。在 24 个月时，70 名接受奥法木单抗治疗的参与者中有 53 名（76%）复发，而 70 名接受利妥昔单抗治疗的参与者中有 46 名（66%）复发（OR，1.6；95%CI，0.8 至 3.3）。两组 B 细胞亚群重建情况相似，不良事件无差异。
单次剂量的奥法木单抗在维持激素依赖和钙调磷酸酶抑制剂依赖型肾病综合征儿童缓解方面并不优于单次剂量的利妥昔单抗。
ClinicalTrials.gov（NCT02394119）和 https://www.clinicaltrialsregister.eu/ctr-search/search（2015-000624-28）。
