Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
Rituximab versus cyclophosphamide for ANCA-associated vasculitis.
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DOI：
10.1056/nejmoa0909905
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发表时间：
2010-07-15
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影响因子：
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通讯作者：
RAVE-ITN Research Group
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作者：
Stone JH;Merkel PA;Spiera R;Seo P;Langford CA;Hoffman GS;Kallenberg CG;St Clair EW;Turkiewicz A;Tchao NK;Webber L;Ding L;Sejismundo LP;Mieras K;Weitzenkamp D;Ikle D;Seyfert-Margolis V;Mueller M;Brunetta P;Allen NB;Fervenza FC;Geetha D;Keogh KA;Kissin EY;Monach PA;Peikert T;Stegeman C;Ytterberg SR;Specks U;RAVE-ITN Research Group
40年来，环磷酰胺和糖皮质激素一直是严重抗中性粒细胞细胞质抗体（ANCA）相关血管炎缓解诱导治疗的基础。非对照研究表明，利妥昔单抗是有效的，可能比环磷酰胺为基础的方案更安全。我们进行了一项多中心、随机、双盲、双假、非劣效性试验，将利妥昔单抗（每周每平方米体表面积375 mg，持续4周）与环磷酰胺（每天每公斤体重2 mg）进行比较，以诱导缓解。糖皮质激素逐渐减少；主要终点是6个月时不使用强的松的疾病缓解。9个中心招募了197名患有韦格纳肉芽肿病或显微镜下多血管炎的anca阳性患者。在两个治疗组中，基线疾病活动度、器官受累程度和复发患者比例相似。利妥昔单抗组中有63例患者（64%）达到了主要终点，而对照组中有52例患者（53%）达到了主要终点，结果符合非劣效性标准（P<0.001）。以利妥昔单抗为基础的方案比以环磷酰胺为基础的方案更有效地诱导复发性疾病缓解；利妥昔单抗组51例患者中有34例（67%）达到主要终点，对照组50例患者中有21例（42%）达到主要终点（P = 0.01）。利妥昔单抗在治疗重大肾脏疾病或肺泡出血患者方面也与环磷酰胺一样有效。在不良事件发生率方面，两组间无显著差异。在诱导严重anca相关血管炎缓解方面，利妥昔单抗治疗并不逊于每日环磷酰胺治疗，在复发性疾病方面可能更优。（由美国国家过敏和传染病研究所、Genentech和Biogen资助；ClinicalTrials.gov编号：NCT00104299。）
Cyclophosphamide and glucocorticoids have been the cornerstone of remission-induction therapy for severe antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis for 40 years. Uncontrolled studies suggest that rituximab is effective and may be safer than a cyclophosphamide-based regimen. We conducted a multicenter, randomized, double-blind, double-dummy, noninferiority trial of rituximab (375 mg per square meter of body-surface area per week for 4 weeks) as compared with cyclophosphamide (2 mg per kilogram of body weight per day) for remission induction. Glucocorticoids were tapered off; the primary end point was remission of disease without the use of prednisone at 6 months. Nine centers enrolled 197 ANCA-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis. Baseline disease activity, organ involvement, and the proportion of patients with relapsing disease were similar in the two treatment groups. Sixty-three patients in the rituximab group (64%) reached the primary end point, as compared with 52 patients in the control group (53%), a result that met the criterion for noninferiority (P<0.001). The rituximab-based regimen was more efficacious than the cyclophosphamide-based regimen for inducing remission of relapsing disease; 34 of 51 patients in the rituximab group (67%) as compared with 21 of 50 patients in the control group (42%) reached the primary end point (P = 0.01). Rituximab was also as effective as cyclophosphamide in the treatment of patients with major renal disease or alveolar hemorrhage. There were no significant differences between the treatment groups with respect to rates of adverse events. Rituximab therapy was not inferior to daily cyclophosphamide treatment for induction of remission in severe ANCA-associated vasculitis and may be superior in relapsing disease. (Funded by the National Institutes of Allergy and Infectious Diseases, Genentech, and Biogen; ClinicalTrials.gov number, NCT00104299.)