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[利妥昔单抗治疗儿童激素依赖型肾病综合征:一家三级医院的研究]

[Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: a tertiary hospital].

作者信息

Guzmán Morais Beatriz, Ordóñez Álvarez Flor Ángel, Santos Rodríguez Fernando, Martín Ramos Silvia, Fernández Novo Gema

机构信息

Servicio de Pediatría, Hospital Clínico Universitario de Valencia, Valencia, España.

Servicio de Nefrología Infantil, Hospital Universitario Central de Asturias, Oviedo, Asturias, España.

出版信息

An Pediatr (Engl Ed). 2021 Jan 28. doi: 10.1016/j.anpedi.2020.12.010.

Abstract

BACKGROUND

Corticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology.

METHODS

Retrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease.

RESULTS

The study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD 19%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10.3 months (median; range 6.5-16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3.6 relapses/year in the previous year to the start of the treatment vs. 0.1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83.3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87.5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96.5% decrease in the corticosteroids doses administered (28.5 mg/m/day during the 3 months pre-treatment vs. 1 mg/m/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46.5 months, range 5-97 months).

CONCLUSION

The favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

摘要

背景

皮质类固醇在肾病综合征的治疗中发挥着核心作用。对于那些对类固醇产生依赖的患者,其管理较为复杂,涉及不同的免疫抑制药物方案。抗CD20单克隆抗体利妥昔单抗,对于类固醇依赖型肾病综合征且病情难以缓解的患者可能具有有益效果,即便我们无法明确其在这种影响中的具体作用。我们呈现过去几年使用此药物治疗儿科患者的个人经验,以全面概述利妥昔单抗在该病症中的作用并提供有用信息。

方法

对西班牙一家三级医院儿科肾病科收治的类固醇依赖型特发性肾病综合征患者进行回顾性研究,这些患者在疾病发展过程中的任何时刻至少接受过一个周期的利妥昔单抗治疗。

结果

该研究纳入8例患者。他们此前均接受过免疫抑制治疗。利妥昔单抗通过静脉输注给药,剂量为375mg/m²,所有剂量均在疾病缓解期给药。除1例淋巴细胞计数为1%的患者外,首次注射利妥昔单抗后均证实B淋巴细胞(CD19%)减少。淋巴细胞减少期持续10.3个月(中位数;范围6.5 - 16个月),在此期间仅有1例患者疾病复发。治疗开始后患者的复发次数有所减少(治疗开始前一年复发3.6次/年,利妥昔单抗治疗后第一年复发0.1次/年)。在复发不止一次的患者中(占患者的75%),第一年无复发生存率达到83.3%,2例患者治疗开始后未复发。利妥昔单抗第一个周期后,87.5%的患者可停用一种或多种药物。利妥昔单抗治疗后,所使用的皮质类固醇剂量降低了96.5%(治疗前3个月为28.5mg/m²/天,患者监测的最后3个月为1mg/m²/天)。利妥昔单抗治疗后监测期(中位数46.5个月,范围5 - 97个月)未观察到归因于该药物的明显不良反应。

结论

我们患者接受利妥昔单抗治疗后报告的良好结果似乎证实了该药物在类固醇依赖型肾病综合征中的有效性,使该治疗选择值得考虑,并使该药物在涉及儿科患者的复杂病例中的使用合法化。即便如此,似乎仍建议开展相关研究,以明确治疗的最佳方案(剂量、间隔和周期)、临床影响以及长期潜在不良反应等问题。

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