Division of Nephrology and Rheumatology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan.
Department of Pediatrics, Tokyo Medical and Dental University, Tokyo, Japan.
Pediatr Nephrol. 2021 Mar;36(3):611-619. doi: 10.1007/s00467-020-04771-5. Epub 2020 Sep 30.
Rituximab is effective for maintaining remission in patients with complicated nephrotic syndrome, although a history of steroid-resistant nephrotic syndrome (SRNS) is a risk factor for early relapse. We investigated the efficacy of prophylactic rituximab treatment for maintaining remission after B cell recovery.
Patients with complicated steroid-dependent or frequently relapsing nephrotic syndrome with history of SRNS who received a single dose of rituximab (375 mg/m) and continued immunosuppressive agents were enrolled in this retrospective study. Patients were divided into two groups: a prophylaxis group, which received additional rituximab treatment at B cell recovery and a non-prophylaxis group. The relapse-free period from the last rituximab infusion (the second treatment in prophylaxis group and the first treatment in non-prophylaxis group) was compared between two groups using the Kaplan-Meier method, and risk factors for early relapse were calculated using multivariate analysis by Cox proportional hazards model.
Sixteen patients in the prophylaxis group and 45 in the non-prophylaxis group were enrolled. Fifty-percent relapse-free survival after the last rituximab treatment was 667 days in the former and 335 days in the latter (p = 0.001). Multivariate analysis showed that additional rituximab treatment was the only significant negative factor for early relapse, with a hazard ratio of 0.40 (p = 0.02). Fifty-percent relapse-free survival after B cell recovery was much longer in the prophylaxis group (954 vs. 205.5 days, p = 0.003).
Additional rituximab treatment at B cell recovery can maintain prolonged remission even after B cell recovery in patients with complicated nephrotic syndrome with history of SRNS.
利妥昔单抗可有效维持复杂性肾病综合征患者的缓解,但类固醇抵抗性肾病综合征(SRNS)病史是早期复发的危险因素。我们研究了 B 细胞恢复后预防性利妥昔单抗治疗维持缓解的疗效。
本回顾性研究纳入了接受单次利妥昔单抗(375mg/m)治疗且继续接受免疫抑制剂治疗的有 SRNS 病史的复杂性激素依赖性或频繁复发肾病综合征患者。患者分为两组:预防组在 B 细胞恢复时接受额外的利妥昔单抗治疗,非预防组则在首次治疗时接受利妥昔单抗治疗。采用 Kaplan-Meier 法比较两组从最后一次利妥昔单抗输注(预防组的第二次治疗和非预防组的第一次治疗)到复发的无复发生存期,采用 Cox 比例风险模型进行多因素分析以确定早期复发的危险因素。
预防组 16 例,非预防组 45 例。前者最后一次利妥昔单抗治疗后 50%无复发生存期为 667 天,后者为 335 天(p = 0.001)。多因素分析显示,额外的利妥昔单抗治疗是早期复发的唯一显著负性因素,风险比为 0.40(p = 0.02)。预防组 B 细胞恢复后的 50%无复发生存期明显更长(954 天 vs. 205.5 天,p = 0.003)。
对于有 SRNS 病史的复杂性肾病综合征患者,在 B 细胞恢复后进行额外的利妥昔单抗治疗可在 B 细胞恢复后维持长时间缓解。