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利妥昔单抗作为抗中性粒细胞胞浆抗体相关血管炎的挽救治疗:15例患者的单中心经验

Rituximab as rescue therapy in anti-neutrophil cytoplasmic antibody-associated vasculitis: a single-centre experience with 15 patients.

作者信息

Lovric Svjetlana, Erdbruegger Uta, Kümpers Philipp, Woywodt Alexander, Koenecke Christian, Wedemeyer Heiner, Haller Hermann, Haubitz Marion

机构信息

Department of Nephrology, Hannover Medical School, Hannover, Germany.

出版信息

Nephrol Dial Transplant. 2009 Jan;24(1):179-85. doi: 10.1093/ndt/gfn430. Epub 2008 Aug 6.

Abstract

BACKGROUND

B-cell depletion with rituximab, a chimeric anti-CD20 antibody, is a novel treatment for refractory and relapsing ANCA-associated small-vessel vasculitis. Data are limited and most reports describe single patients or small numbers of patients followed prospectively.

METHODS

We report a single-centre experience with 15 patients who received rituximab for refractory or relapsing ANCA-associated vasculitis. All patients had been treated with corticosteroids and cyclophosphamide and a variety of other second-line immunosuppressive agents. None of the patients had evidence of infection and received four infusions of 375 mg/m(2) of rituximab. Disease activity was assessed in accordance with the Birmingham Vasculitis Activity Score (BVAS). BVAS, C-reactive protein and ANCA titres were recorded at baseline and during follow-up.

RESULTS

B-cell depletion was achieved in all patients. Partial or complete remission was seen in 14 of 15 patients with a significant decline in BVAS compared to baseline (P < 0.007). One patient with granulomatous ANCA-associated vasculitis did not respond to rituximab. There were no side effects during rituximab infusion. Transient leucopenia was observed in two patients. One patient with bronchial stenosis died of pneumonia 5.5 months after the initiation of rituximab treatment. One initially anti-HBc-positive/HBsAg-negative patient experienced a reactivation of hepatitis B, developed end-stage renal failure and died after refusal of dialysis.

CONCLUSIONS

We report the largest case series of rituximab use for ANCA-associated vasculitis so far. Our data support that the drug is capable of inducing partial or complete remission in refractory or relapsing patients. Leucopenia and infectious complications remain a matter of concern.

摘要

背景

利妥昔单抗是一种嵌合抗CD20抗体,可使B细胞耗竭,是难治性和复发性抗中性粒细胞胞浆抗体(ANCA)相关小血管炎的一种新疗法。相关数据有限,大多数报告描述的是单个患者或前瞻性随访的少数患者。

方法

我们报告了15例接受利妥昔单抗治疗难治性或复发性ANCA相关血管炎的单中心经验。所有患者均接受过皮质类固醇、环磷酰胺及多种其他二线免疫抑制剂治疗。所有患者均无感染证据,接受了4次375mg/m²的利妥昔单抗输注。根据伯明翰血管炎活动评分(BVAS)评估疾病活动度。在基线和随访期间记录BVAS、C反应蛋白和ANCA滴度。

结果

所有患者均实现了B细胞耗竭。15例患者中有14例出现部分或完全缓解,与基线相比BVAS显著下降(P<0.007)。1例肉芽肿性ANCA相关血管炎患者对利妥昔单抗无反应。利妥昔单抗输注期间无副作用。2例患者出现短暂性白细胞减少。1例支气管狭窄患者在利妥昔单抗治疗开始5.5个月后死于肺炎。1例最初抗HBc阳性/HBsAg阴性的患者出现乙型肝炎再激活,发展为终末期肾衰竭,在拒绝透析后死亡。

结论

我们报告了迄今为止利妥昔单抗用于ANCA相关血管炎的最大病例系列。我们的数据支持该药物能够在难治性或复发性患者中诱导部分或完全缓解。白细胞减少和感染并发症仍然值得关注。

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