15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis:: A six-month open-label trial to evaluate safety and efficacy
15-Deoxyspergualin in patients with refractory ANCA-associated systemic vasculitis:: A six-month open-label trial to evaluate safety and efficacy
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DOI：
10.1097/01.asn.0000048716.42876.14
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发表时间：
2003-02-01
影响因子：
13.6
通讯作者：
Van der Woude, FJ
中科院分区：
文献类型：
--
作者：
Birck, R;Warnatz, K;Van der Woude, FJ
环磷酰胺（CYC）和口服糖皮质激素的组合是有效的，在大多数患者与抗中性粒细胞胞质抗体相关性血管炎（AASV），但它具有很大的风险，药物相关的发病率和死亡率。需要新的治疗方案，特别是在难治性病例中。免疫抑制剂15-脱氧精胍菌素（DSG）在实验性自身免疫性疾病和移植以及人类肾移植急性排斥反应中是有效的。为了评估DSG的疗效和安全性，在对标准免疫抑制剂无反应或有禁忌症的AASV患者中进行了一项开放标签多中心试验。包括19例韦格纳肉芽肿病和1例显微镜下多血管炎。其中9人在进入研究前不久接受了CYC治疗，但没有明显的治疗成功。DSG（0.5 mg/kg/d）给药2 - 3周，直至WBC计数降至3000/穆尔，然后停药，直至WBC再次达到至少4000/穆尔。这被重复多达六个循环。研究期间，除类固醇外，不允许使用其他免疫抑制剂。在DSG治疗期间，70%的病例（6例完全缓解; 8例部分缓解）实现了疾病改善。每例患者在周期内均定期发生白细胞减少症，无一例例外均为一过性。未观察到死亡或败血症。观察到轻度至中度感染，主要发生在呼吸道，但在充分治疗下消退，无后遗症。结论：在严密监测白细胞计数的情况下，DSG治疗难治性韦格纳肉芽肿是成功的。
The combination of cyclophosphamide (CYC) and oral corticosteroids is effective in the majority of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AASV), but it carries substantial risk of drug-related morbidity and mortality. New regimens are desired, especially in refractory cases. The immunosuppressant 15-deoxyspergualin (DSG) is effective in experimental autoimmune disease and transplantation as well as in acute kidney transplant rejection in humans. To assess the efficacy and safety of DSG, an open label multicenter trial was conducted in patients with AASV who were either unresponsive or had contraindications for standard immunosuppressants. Included were 19 cases of Wegener granulomatosis and one case of microscopic polyangiitis. Nine of them had received CYC shortly before study entry without apparent therapeutic success. DSG (0.5 mg/kg per d) was given for 2 to 3 wk until the WBC count dropped to 3000/mul followed by a rest until at least a WBC of 4000/mul was reached again. This was repeated up to six cycles. During the study, no other immunosuppressants besides steroids were allowed. Disease improvement during treatment with DSG was achieved in 70% of cases (six cases of complete remission; eight cases of partial remission). Leucopenia occurred in each patient in a regular pattern during the cycles and was transient without exception. No mortality or septicemia was observed. Mild to moderate infections mainly in the respiratory tract were observed but resolved under adequate treatment without sequel. It is concluded that treatment with DSG is successful in patients with refractory Wegener granulomatosis under careful monitoring of WBC count.