低剂量利妥昔单抗治疗儿童肾病综合征疗效及安全性的前瞻性随机对照研究

Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial

摘要:

目的 对比利妥昔单抗（rituximab，RTX）低剂量（200 mg/m²）与推荐剂量（375 mg/m²）重复使用治疗频复发型肾病综合征（frequently relapsing nephrotic syndrome，FRNS）或激素依赖型肾病综合征（steroid-dependent nephrotic syndrome，SDNS）维持缓解的疗效和安全性。方法 采用随机对照试验研究法，选择2020年9月—2021年12月在安徽省儿童医院儿童肾脏科接受系统治疗的29例FRNS/SDNS患儿为研究对象，按随机数字表法分为推荐剂量组（n=14）和低剂量组（n=15）。分析比较两组患儿的一般特征、RTX治疗前后CD19变化、复发次数、糖皮质激素使用剂量、RTX不良反应及住院费用等差异。结果 与治疗前相比，低剂量组与推荐剂量组在应用RTX后均能使B淋巴细胞耗竭，且复发次数减少、糖皮质激素使用剂量下降（P<0.05）。低剂量组RTX治疗后的临床疗效与推荐剂量组相当（P>0.05）；而低剂量组第2~4次住院费用下降（P<0.05）。两组在使用RTX过程中及后期随访中无严重不良反应，发生的不良反应差异无统计学意义（P>0.05）。结论 低剂量与推荐剂量重复RTX治疗临床疗效和安全性相当，可显著降低FRNS/SDNS复发次数及糖皮质激素使用剂量，在整个治疗周期内无明显不良反应，适合临床推广。

Abstract:

Objective To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m²) versus the recommended dose (375 mg/m²) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS).Methods A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs.Results After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05).Conclusions Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.