甲氨蝶呤与环磷酰胺用于抗中性粒细胞胞浆抗体相关性血管炎缓解期维持治疗的随机试验
Methotrexate versus cyclophosphamide for remission maintenance in ANCA-associated vasculitis: A randomised trial.
作者信息
Maritati Federica, Alberici Federico, Oliva Elena, Urban Maria L, Palmisano Alessandra, Santarsia Francesca, Andrulli Simeone, Pavone Laura, Pesci Alberto, Grasselli Chiara, Santi Rosaria, Tumiati Bruno, Manenti Lucio, Buzio Carlo, Vaglio Augusto
机构信息
Nephrology Unit, University Hospital of Parma, Italy.
Nephrology and Immunology Unit, ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, Milano, Italy.
出版信息
PLoS One. 2017 Oct 10;12(10):e0185880. doi: 10.1371/journal.pone.0185880. eCollection 2017.
OBJECTIVES
The treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is based on remission-induction and remission-maintenance. Methotrexate is a widely used immunosuppressant but only a few studies explored its role for maintenance in AAV. This trial investigated the efficacy and safety of methotrexate as maintenance therapy for AAV.
METHODS
In this single-centre, open-label, randomised trial we compared methotrexate and cyclophosphamide for maintenance in AAV. We enrolled patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), the latter with poor-prognosis factors and/or peripheral neuropathy. Remission was induced with cyclophosphamide. At remission, the patients were randomised to receive methotrexate or to continue with cyclophosphamide for 12 months; after treatment, they were followed for another 12 months. The primary end-point was relapse; secondary end-points included renal outcomes and treatment-related toxicity.
RESULTS
Of the 94 enrolled patients, 23 were excluded during remission-induction or did not achieve remission; the remaining 71 were randomised to cyclophosphamide (n = 33) or methotrexate (n = 38). Relapse frequencies at months 12 and 24 after randomisation were not different between the two groups (p = 1.00 and 1.00). Relapse-free survival was also comparable (log-rank test p = 0.99). No differences in relapses were detected between the two treatments when GPA+MPA and EGPA were analysed separately. There were no differences in eGFR at months 12 and 24; proteinuria declined significantly (from diagnosis to month 24) only in the cyclophosphamide group (p = 0.0007). No significant differences in adverse event frequencies were observed.
CONCLUSIONS
MTX may be effective and safe for remission-maintenance in AAV.
TRIAL REGISTRATION
clinicaltrials.gov NCT00751517.
目的
抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）的治疗基于诱导缓解和维持缓解。甲氨蝶呤是一种广泛使用的免疫抑制剂，但仅有少数研究探讨了其在AAV维持治疗中的作用。本试验研究了甲氨蝶呤作为AAV维持治疗的疗效和安全性。
方法
在这项单中心、开放标签、随机试验中，我们比较了甲氨蝶呤和环磷酰胺在AAV维持治疗中的效果。我们纳入了患有肉芽肿性多血管炎（GPA）、显微镜下多血管炎（MPA）和嗜酸性肉芽肿性多血管炎（EGPA）的患者，后者具有预后不良因素和/或周围神经病变。采用环磷酰胺诱导缓解。在缓解期，将患者随机分组，分别接受甲氨蝶呤或继续使用环磷酰胺治疗12个月；治疗后，对他们进行另外12个月的随访。主要终点是复发；次要终点包括肾脏结局和治疗相关毒性。
结果
94名纳入患者中，23名在诱导缓解期间被排除或未达到缓解；其余71名被随机分为环磷酰胺组（n = 33）或甲氨蝶呤组（n = 38）。随机分组后第12个月和第24个月时，两组的复发频率无差异（p = 1.00和1.00）。无复发生存率也相当（对数秩检验p = 0.99）。分别分析GPA + MPA和EGPA时，两种治疗方法的复发情况无差异。第12个月和第24个月时估算肾小球滤过率（eGFR）无差异；仅环磷酰胺组蛋白尿显著下降（从诊断到第24个月）（p = 0.0007）。不良事件发生频率无显著差异。
结论
甲氨蝶呤在AAV维持缓解治疗中可能有效且安全。
试验注册
clinicaltrials.gov NCT00751517。
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