Retrospective single-arm cohort study of steroid-dependent minimal change nephrotic syndrome treated with very low-dose rituximab
Retrospective single-arm cohort study of steroid-dependent minimal change nephrotic syndrome treated with very low-dose rituximab
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DOI：
10.5414/cn110245
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发表时间：
2021-01-01
影响因子：
1.1
通讯作者：
Yokoyama, Hitoshi
中科院分区：
文献类型：
--
作者：
Fujimoto, Keiji;Kagaya, Yu;Yokoyama, Hitoshi
目的：关于成人类固醇依赖性最小改变肾病综合征（MCNS）患者维持缓解和减少免疫抑制剂依赖的最佳利妥昔单抗（RTX）剂量的结论不一致。我们报告了第一次低剂量（< 375 mg/m(2) BSA） RTX治疗，每6个月给药一次。材料和方法：在这项回顾性单臂队列研究中，我们研究了低剂量RTX治疗减少并最终停止强的松龙（PSL）和环孢素（CyA）治疗的安全性和有效性。选择13例类固醇依赖性MCNS患者（8男5女，年龄16 - 65岁，中位治疗史8年，12例同时服用CyA）在低剂量RTX （200 mg/体）给药后维持缓解。结果：首次RTX给药后，受试者观察的中位时间为34个月（累计RTX剂量：400 - 1400 mg）。RTX在每个受试者的最后观察期间显著降低了PSL和CyA的剂量（中位剂量：PSL 15->0 mg/天，p = 0.0002; CyA 80->0 mg/天，p = 0.0005）。停用两种药物后，所有患者均保持完全缓解，中位完全缓解（CR）维持期为25个月。一名患者在第一次RTX剂量后出现复发，但暂时增加PSL和CyA剂量恢复了缓解。未观察到严重的rtx相关不良反应。即使MCNS缓解，90.5%的患者外周血cd19阳性细胞计数也没有减少。结论：低剂量RTX治疗在类固醇依赖性MCNS患者维持缓解和减少免疫抑制剂剂量方面似乎有效，这可能涉及b细胞非依赖性机制。
Aim: Conclusions regarding the best rituximab (RTX) dose to maintain remission and reduce immunosuppressant dependence in adult patients with steroid-dependent minimal change nephrotic syndrome (MCNS) are inconsistent. We report the first low-dose (< 375 mg/m(2) BSA) RTX therapy, administered once every 6 months. Materials and methods: In this retrospective single-arm cohort study, we investigated the safety and efficacy of low-dose RTX therapy to reduce and ultimately stop prednisolone (PSL) and cyclosporine (CyA) treatment. 13 patients (8 men and 5 women; aged 16 - 65 years; 8-year median treatment history; 12 patients concurrently taking CyA) with steroid-dependent MCNS were chosen to maintain remission following low-dose RTX (200 mg/body) administration. Results: The median period of subject observation following the first RTX dosing was 34 months (cumulative RTX dose: 400 - 1,400 mg). RTX significantly reduced PSL and CyA doses during the final observation in each subject (median dose: PSL 15->0 mg/day, p = 0.0002; CyA 80->0 mg/day, p = 0.0005). All patients maintained complete remission after discontinuing both drugs for a median complete remission (CR) maintenance period of 25 months. One patient showed relapse following the first RTX dose, but a temporary increase in PSL and CyA dose restored the remission. No serious RTX-related adverse effects were observed. Even with MCNS remission, peripheral CD19-positive cell count was not depleted in 90.5% of all cases. Conclusion: Low-dose RTX therapy appears to be effective in maintaining remission and reducing immunosuppressant doses in patients with steroid-dependent MCNS, which might involve a B-cell-independent mechanism.