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抗CD20单克隆抗体(利妥昔单抗)治疗冷球蛋白血症性血管炎:我们目前的进展如何?

Anti-CD20 monoclonal antibody (rituximab) treatment for cryoglobulinemic vasculitis: where do we stand?

作者信息

Cacoub P, Delluc A, Saadoun D, Landau D A, Sene D

机构信息

Université Pierre et Marie Curie Paris 6, CNRS, UMR 7087, Paris, France.

出版信息

Ann Rheum Dis. 2008 Mar;67(3):283-7. doi: 10.1136/ard.2006.065565. Epub 2007 Jul 20.

Abstract

Mixed cryoglobulinemia (MC) vasculitis represents a complication of the B cell response to a variety of chronic inflammatory diseases. Recent reports describe the use of monoclonal antibodies directed to CD20 antigen (rituximab), a transmembrane protein expressed on pre-B lymphocytes and mature lymphocytes. The goal of this article is therefore to review published data in order to better analyse the efficacy and tolerance of rituximab treatment in patients with MC vasculitis. After systematic review of the literature and exclusion of review papers, 13 manuscripts were identified that reported on a total number of 57 cases of MC secondary to hepatitis C virus (HCV) infection (75.4%) or essential mixed cryoglobulinemia (24.6%). Previous treatments failed to control the main signs of vasculitis; these were either HCV (n = 37) or immunomodulating treatments. Most patients (48 out of 57) received four weekly consecutive intravenous infusions of 375 mg/m(2) of rituximab. The duration of follow-up after rituximab therapy was 9.7 months. Rituximab infusions had great efficacy on the main vasculitis signs, with a clinical response in 80-93% patients. A relapse of MC was noted in 14 out of 36 (39%) patients. A relatively small number of side effects were reported. We conclude that rituximab therapy for patients with mixed cryoglobulinemia vasculitis, HCV-induced or essential, shows great efficacy on the main vasculitis signs in the majority of reported patients. A relapse of cryoglobulinemia vasculitis was frequently noted. Randomised controlled trials with long-term study are needed to form definitive conclusions on the benefit/risk ratio of rituximab therapy in such patients.

摘要

混合性冷球蛋白血症(MC)血管炎是B细胞对多种慢性炎症性疾病产生反应的一种并发症。近期报告描述了针对CD20抗原(利妥昔单抗)的单克隆抗体的使用情况,CD20抗原是一种在前B淋巴细胞和成熟淋巴细胞上表达的跨膜蛋白。因此,本文的目的是回顾已发表的数据,以便更好地分析利妥昔单抗治疗MC血管炎患者的疗效和耐受性。在对文献进行系统回顾并排除综述性论文后,确定了13篇手稿,这些手稿共报告了57例继发于丙型肝炎病毒(HCV)感染(75.4%)或原发性混合性冷球蛋白血症(24.6%)的MC病例。先前的治疗未能控制血管炎的主要症状;这些治疗包括针对HCV的治疗(n = 37)或免疫调节治疗。大多数患者(57例中的48例)连续四周每周静脉输注375 mg/m²的利妥昔单抗。利妥昔单抗治疗后的随访时间为9.7个月。利妥昔单抗输注对主要血管炎症状有显著疗效,80 - 93%的患者有临床反应。36例患者中有14例(39%)出现MC复发。报告的副作用相对较少。我们得出结论,对于HCV诱导型或原发性混合性冷球蛋白血症血管炎患者,利妥昔单抗治疗对大多数报告患者的主要血管炎症状显示出显著疗效。冷球蛋白血症血管炎复发情况较为常见。需要进行长期研究的随机对照试验,以就利妥昔单抗治疗此类患者的获益/风险比得出明确结论。

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