甲氨蝶呤和低剂量强的松治疗特发性腹膜后纤维化：一项随机临床试验

IF 7 1区医学 Q1 IMMUNOLOGY

Journal of autoimmunity Pub Date : 2025-09-19 DOI:10.1016/j.jaut.2025.103487

Francesco Peyronel , Alessandra Palmisano , Federica Maritati , Federico Alberici , Maria L. Urban , Davide Gianfreda , Giovanni M. Rossi , Paride Fenaroli , Alessandra Bettiol , Gabriella Moroni , Augusto Vaglio

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引用次数: 0

摘要

目的探讨甲氨蝶呤联合小剂量强的松治疗特发性腹膜后纤维化的疗效和安全性。方法：我们进行了一项开放标签、随机、主动对照、非劣效性的III期试验。在两个意大利中心（帕尔马大学医院肾病科和米兰Policlinico医院）的门诊登记了60名（78名筛查对象中）新诊断为特发性腹膜后纤维化，肾小球滤过率估计为30 mL/min/1.73 m2的成年人。患者被随机分配（1:1）接受低剂量强的松加甲氨蝶呤（MTX + LowPred）或标准剂量强的松单独（standPred）治疗9个月。主要终点是第9个月的缓解。缓解定义为无症状和输尿管梗阻（无支架或肾造口），急性期反应物正常；次要终点包括RPF厚度减少、复发和治疗相关毒性。结果MTX +低剂量治疗组29例，标准剂量治疗组31例。26例（89.7%）接受MTX + LowPred治疗的患者和25例（80.6%）接受standPred治疗的患者达到并维持缓解至第9个月。缓解率的差异为9.1% (95% CI - 9.9% - 27.3%)，符合非劣效性标准。缓解时间相似（log-rank检验p = 0.549）。两组RPF厚度减少和复发率相当。standPred组中位累积泼尼松剂量显著高于standPred组（p < 0.001）。两组不良事件发生率无显著差异。结论低剂量强的松加甲氨蝶呤方案在特发性腹膜后纤维化缓解方面不逊于标准剂量强的松，可显著减少糖皮质激素暴露。临床试验注册：NCT01240850。

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Methotrexate and low-dose prednisone in idiopathic retroperitoneal fibrosis: a randomised clinical trial

Objectives

To test the efficacy and safety of methotrexate plus low-dose prednisone in patients with idiopathic retroperitoneal fibrosis.

Methods

We conducted an open-label, randomised, active-controlled, non-inferiority phase III trial. Sixty (out of 78 screened) adults with newly diagnosed idiopathic retroperitoneal fibrosis and an estimated glomerular filtration rate >30 mL/min/1.73 m² were enrolled at outpatient clinics of two Italian centres (Nephrology units of Parma University Hospital and Milano Policlinico Hospital). Patients were randomly assigned (1:1) to receive low-dose prednisone plus methotrexate (MTX + LowPred) or standard-dose prednisone alone (standPred) for nine months. The primary endpoint was remission at month 9. Remission was defined as absence of symptoms and ureteral obstruction (free of stents or nephrostomies), and normal acute-phase reactants; secondary endpoints included reduction in RPF thickness, relapses and treatment-related toxicity.

Results

29 patients received MTX + LowPred and 31 standPred. Twenty-six patients (89.7 %) receiving MTX + LowPred and 25 (80.6 %) receiving standPred achieved and maintained remission until month 9. The difference between remission rates was 9.1 % (95 %CI -9.9 %–27.3 %), meeting the criterion for non-inferiority. Time-to-remission was similar (log-rank test p = 0.549). The two groups showed comparable RPF thickness reduction and relapse rates. The median cumulative prednisone dose was significantly higher in the standPred group (p < 0.001). No significant differences in adverse events were observed.

Conclusions

A low-dose prednisone plus methotrexate regimen is non-inferior to standard-dose prednisone in achieving remission in idiopathic retroperitoneal fibrosis, allowing significant reduction in glucocorticoid exposure.

Trial registration

ClinicalTrials.gov: NCT01240850.

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来源期刊

Journal of autoimmunity 医学-免疫学

CiteScore

27.90

自引率

1.60%

发文量

117

审稿时长

17 days

期刊介绍： The Journal of Autoimmunity serves as the primary publication for research on various facets of autoimmunity. These include topics such as the mechanism of self-recognition, regulation of autoimmune responses, experimental autoimmune diseases, diagnostic tests for autoantibodies, as well as the epidemiology, pathophysiology, and treatment of autoimmune diseases. While the journal covers a wide range of subjects, it emphasizes papers exploring the genetic, molecular biology, and cellular aspects of the field. The Journal of Translational Autoimmunity, on the other hand, is a subsidiary journal of the Journal of Autoimmunity. It focuses specifically on translating scientific discoveries in autoimmunity into clinical applications and practical solutions. By highlighting research that bridges the gap between basic science and clinical practice, the Journal of Translational Autoimmunity aims to advance the understanding and treatment of autoimmune diseases.