摘要（德国） 背景 最近的对照研究显示，利妥昔单抗（RTX）与标准环磷酰胺缓解诱导治疗ANCA相关性血管炎的疗效相当，且有几项非对照研究提示，RTX对难治性ANCA相关性血管炎有效。 目的 通过单中心回顾性研究RTX对75例难治性WG患者的总体疗效，对比其对肉芽肿与血管炎表现的疗效。

方法 所有患者满足WG的ACR标准，查阅从2002年到2010年使用或未用过常规免疫抑制剂治疗的难治性WG，分析RTX治疗(4x 375 mg/m2 4次，每周1次)前后的器官表现、疾病活动性、ANCA滴度和B细胞计数。记录副作用、缓解期和复发情况。根据EULAR和伯明翰血管炎活动性得分判断疾病阶段和活动性。

结果 59例WG患者接受了75个疗程的RTX治疗，主要针对其难治性表现（66%因肉芽肿和（或）39%因血管炎）。随访至少4个月，9.33%完全缓解，52%部分缓解，9.33%活动性不变，26.66%疾病进展。RTX治疗后强的松龙量、伯明翰血管炎活动性得分和B细胞计数明显降低(p<0 .05)。与肉芽肿表现如眶内肉芽肿和硬脑膜炎相比，血管炎表现的有效率（完全缓解加部分缓解）明显增高 (p<0.05)，肺泡出血(n="12)或难治性活动性肾病(n=26)的有效率分别为83.3%和80.1%，而27例眼眶肉芽肿中，无1例完全缓解者，44.4%部分缓解," 22.2%无改变，33.3%有进展，2例缓解死亡，感染率21%，复发多[平均随访13.5个月（3-54个月），40%复发]，复发后再次治疗有效。

结论 RTX对难治性WG的总体疗效好，完全缓解或改善率为61.3%，血管炎表现的有效率高，治疗无效或进展主要出现在肉芽肿表现，尤其是眶内肉芽肿，复发率高（40%）。

附原文 Background: A recent controlled study demonstrated equal efficacy of RTX compared to cyclophosphamide for standard remission induction in ANCA-associated vasculitis (AAV). Furthermore, several uncontrolled studies suggest efficacy of RTX in refractory AAV.

Objectives: To determine the overall efficacy of RTX in refractory WG in a monocentric retrospective study of 75 cases and to compare the efficacy of RTX in granulomatous versus vasculitic manifestations.Methods: All patients who fulfilled the American College of Rheumatology criteria of WG and who received RTX with or without additional conventional immunosuppressants for refractory WG from 2002 to 2010 were selected for the study and analysed for organ manifestations, disease activity, ANCA titre and B-cell counts before and after RTX treatment (4x 375 mg/m2 four times in weekly intervals). Side effects, duration of remission and relapses were also documented. Disease stages and activity were defined according to EULAR and Birmingham Vasculitis Activity Score.Results: 59 WG patients received 75 cycles of RTX for refractory manifestations, 66% due to granulomatous and/or 39% due to vasculitic manifestations. After a follow-up of at least 4 months, 9.33% had a complete remission, 52% a response, 9.33% an unchanged activity and 26.66% a disease progression. Prednisolone dose, BVAS and B-cell counts decreased significantly (p<0 .05) after rtx treatment. response rates (complete remission plus response) of vasculitic manifestations were excellent and significantly higher compared to granulomatous manifestation such as orbital granuloma and pachymeningitis (p<0.05): in patients with alveolar hemorrhage (n="12)" or refractory active renal disease (n="26)," there were 83.3% and 80.1% complete remissions/responses, whereas in 27 patients with orbital granuloma, there were no complete remissions, 44.4% responses, 22.2% with unchanged activity and 33.3% with progression. 2 patients died, the infection rate was 21% and relapse was frequent (40% after a median follow-up of 13.5 months, range 3-54 months). re-treatment after relapse was effective.conclusions: overall efficacy of rtx in refractory wg was good (around 61.3% complete remissions or improvement). response rates of vasculitic manifestations were excellent; treatment failure or progress occurred mainly in granulomatous manifestations, especially in orbital granuloma. relapse rates were high (40%).

引自：J.U. Holle, C. Mueller, W.L. Gross, E. Csernok, E. Reinhold-Keller. RRETROSPECTIVE STUDY OF RITUXIMAB (RTX) IN REFRACTORY GRANULOMATOSIS WITH POLYANGIITIS (WEGENER'S) (WG): COMPARISON OF TREATMENT RESPONSE IN VASCULITIC VERSUS GRANULOMATOUS MANIFESTATIONS. Ann Rheum Dis 2011;70(Suppl3):85