Pediatric Nephrology Department, Robert Debré Hospital, Assistance publique-Hôpitaux de Paris (APHP), Paris, France.
Pediatric Nephrology Unit, Pellegrin-Enfants Hospital-Bordeaux University, Bordeaux, France.
Pediatr Nephrol. 2018 Jan;33(1):111-116. doi: 10.1007/s00467-017-3767-4. Epub 2017 Aug 5.
In clinical trials, the addition of rituximab (RTX) to the combination therapeutic regimen of mycophenolate mofetil (MMF) and corticosteroids failed to improve outcome in lupus nephritis (LN). However, recent data suggest that RTX may have steroid-sparing beneficial effects with an efficacy similar to that of conventional regimens. We report our experience with RTX in the treatment of children with LN.
Patients treated with RTX for first occurrence of LN class III to V were enrolled in the study. Treatment consisted of methylprednisolone pulse (500 mg/m) followed by RTX (1000 mg/1.73 m) at days 1 and 15, and MMF (1200 mg/m/day). Prednisolone tapering and withdrawal was left to the physician's discretion. Complete remission (CR) was defined as a urine protein-to-creatinine ratio (U Pr/Cr) of <5 mg/mg and normal serum creatinine, and partial remission (PR) as a U Pr/Cr of <30 mg/mg and a <15% rise in serum creatinine over baseline.
Twelve patients were included in the study, with median follow-up of 23.7 [interquartile range (IQR) 12.8-33.5] months. Median age of the patients was 13.6 [12.3-15.1] years, median proteinuria was 32 [19-67] mg/mg and median estimated glomerular filtration rate was 76.1 [59.3-97.7] mL/min/1.73 m. Median CD20 depletion duration was 10 [6.8-11.0] months. Prednisolone was rapidly tapered, with median dose of 0.3 [0.15-0.41], 0.10 [0.09-0.16] and 0.0 [0.0-0.04] mg/kg/day at 3, 6 and 12 months respectively. At 3 months, three and seven patients achieved CR and PR, respectively; at 6 and 12 months all patients achieved remission (9 CR, 3 PR) and none relapsed during follow-up. Five infectious complications were observed, including three varicella-zoster virus (VZV) infections.
In our pediatric patients with LN, therapy with RTX + MMF combined with a rapid decrease in steroid appears to have been an efficacious treatment for severe LN but was associated with high rate of VZV infection. The potential of RTX to allow complete steroid avoidance warrants further investigation in children.
在临床试验中，利妥昔单抗（RTX）联合霉酚酸酯（MMF）和皮质类固醇的联合治疗方案并未改善狼疮肾炎（LN）的结局。然而，最近的数据表明，RTX 可能具有类固醇节约的有益作用，其疗效与传统方案相似。我们报告了 RTX 治疗儿童 LN 的经验。
纳入首次发生 LN III 至 V 级的患者接受 RTX 治疗。治疗包括甲泼尼龙脉冲（500mg/m2），然后在第 1 和 15 天给予 RTX（1000mg/1.73m）和 MMF（1200mg/m/天）。泼尼松龙逐渐减量和停药由医生决定。完全缓解（CR）定义为尿蛋白/肌酐比（U Pr/Cr）<5mg/mg 和正常血清肌酐，部分缓解（PR）定义为 U Pr/Cr<30mg/mg 和血清肌酐较基线升高<15%。
本研究纳入 12 例患者，中位随访时间为 23.7[四分位距（IQR）12.8-33.5]个月。患者中位年龄为 13.6[12.3-15.1]岁，中位蛋白尿为 32[19-67]mg/mg，中位估计肾小球滤过率为 76.1[59.3-97.7]mL/min/1.73m。中位 CD20 耗竭时间为 10[6.8-11.0]个月。泼尼松龙迅速减量，第 3、6 和 12 个月的剂量分别为 0.3[0.15-0.41]、0.10[0.09-0.16]和 0.0[0.0-0.04]mg/kg/天。第 3 个月时，分别有 3 例和 7 例患者达到 CR 和 PR；第 6 和 12 个月时，所有患者均达到缓解（9 例 CR，3 例 PR），随访期间无复发。观察到 5 例感染性并发症，包括 3 例水痘带状疱疹病毒（VZV）感染。
在我们的 LN 儿科患者中，RTX+MMF 联合治疗并迅速减少类固醇的使用似乎是一种有效的治疗严重 LN 的方法，但与高 VZV 感染率相关。RTX 完全避免类固醇的潜力值得进一步研究。
