A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies
A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies
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DOI：
10.1056/nejmoa020286
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发表时间：
2003-07-03
影响因子：
158.5
通讯作者：
Pusey, C
中科院分区：
文献类型：
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作者：
Jayne, D;Rasmussen, N;Pusey, C
背景：原发性系统性血管炎通常与中性粒细胞胞浆抗原自身抗体相关，包括韦格纳肉芽肿病和显微镜下多血管炎。我们调查了是否暴露于环磷酰胺在全身性血管炎的患者可以减少由硫唑嘌呤替代在restriction.METHODS：我们研究了患者的新诊断的全身性血管炎和血清肌酐浓度为5.7毫克每分升（500微摩尔每公升）或less.All患者接受了至少三个月的治疗口服环磷酰胺和泼尼松龙。缓解后，患者被随机分配到继续环磷酰胺治疗（每天每公斤体重1.5毫克）或硫唑嘌呤替代方案（每天每公斤体重2毫克）。两组继续接受泼尼松龙治疗，并从研究开始随访18个月。复发是主要终点。结果：在155例研究患者中，144例（93%）进入缓解期，并被随机分配到硫唑嘌呤（71例）或继续环磷酰胺（73例）。有8人死亡（5%），其中7人在前三个月死亡。硫唑嘌呤组有11例复发（15.5%），环磷酰胺组有10例复发（13.7%，P=0.65）。诱导期有15例患者发生严重不良事件（10%），缓解期硫唑嘌呤组有8例患者发生严重不良事件（11%），缓解期环磷酰胺组有7例患者发生严重不良事件（10%，P=0.94缓解期组间比较）。显微镜下多血管炎患者的复发率低于韦格纳肉芽肿病患者（P=0.03）。结论：在泛发性血管炎患者中，缓解后停用环磷酰胺和硫唑嘌呤替代并不增加复发率。因此，环磷酰胺暴露的持续时间可以安全地缩短。
BACKGROUND:The primary systemic vasculitides usually associated with autoantibodies to neutrophil cytoplasmic antigens include Wegener's granulomatosis and microscopic polyangiitis. We investigated whether exposure to cyclophosphamide in patients with generalized vasculitis could be reduced by substitution of azathioprine at remission.METHODS:We studied patients with a new diagnosis of generalized vasculitis and a serum creatinine concentration of 5.7 mg per deciliter (500 micromol per liter) or less. All patients received at least three months of therapy with oral cyclophosphamide and prednisolone. After remission, patients were randomly assigned to continued cyclophosphamide therapy (1.5 mg per kilogram of body weight per day) or a substitute regimen of azathioprine (2 mg per kilogram per day). Both groups continued to receive prednisolone and were followed for 18 months from study entry. Relapse was the primary end point.RESULTS:Of 155 patients studied, 144 (93 percent) entered remission and were randomly assigned to azathioprine (71 patients) or continued cyclophosphamide (73 patients). There were eight deaths (5 percent), seven of them during the first three months. Eleven relapses occurred in the azathioprine group (15.5 percent), and 10 occurred in the cyclophosphamide group (13.7 percent, P=0.65). Severe adverse events occurred in 15 patients during the induction phase (10 percent), in 8 patients in the azathioprine group during the remission phase (11 percent), and in 7 patients in the cyclophosphamide group during the remission phase (10 percent, P=0.94 for the comparison between groups during the remission phase). The relapse rate was lower among the patients with microscopic polyangiitis than among those with Wegener's granulomatosis (P=0.03).CONCLUSIONS: In patients with generalized vasculitis, the withdrawal of cyclophosphamide and the substitution of azathioprine after remission did not increase the rate of relapse. Thus, the duration of exposure to cyclophosphamide may be safely reduced.