An open study of B lymphocyte depletion in systemic lupus erythematosus
An open study of B lymphocyte depletion in systemic lupus erythematosus
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DOI：
10.1002/art.10541
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发表时间：
2002-10-01
影响因子：
--
通讯作者：
Isenberg, DA
中科院分区：
文献类型：
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作者：
Leandro, MJ;Edwards, JC;Isenberg, DA
Objective.目的探讨B淋巴细胞清除治疗难治性系统性红斑狼疮（SLE）的安全性和有效性。6例对标准免疫抑制治疗耐药的活动性SLE女性患者接受开放标签治疗。在2周的时间内，每例患者接受两次500 mg利妥昔单抗输注，两次750 mg环磷酰胺输注和高剂量口服皮质类固醇。随访期间未观察到明显不良事件。患者1在3个月时没有改善，但随后失访。在6个月时，所有5例剩余患者均得到改善，如不列颠群岛狼疮评估组总体评分从基线时的中位数14（范围9-27）改善至6个月时的中位数6（范围3-8）所证明。SLE的表现，如疲劳、关节痛/关节炎和浆膜炎，对该方案的反应特别好。患者2、3、5和6中的血红蛋白水平升高。患者2、3、4和5的红细胞沉降率降低，患者1稳定。在患者4和5中，尿蛋白/肌酐比值显著降低。所有5例基线水平较低的患者的C3血清水平均升高;其中2例患者（患者2和5）的C3值在6个月时正常。抗双链DNA抗体水平在不同的患者中有不同的变化。本研究为B淋巴细胞耗竭疗法治疗系统性红斑狼疮的安全性和可能有效性提供了足够的证据，以证明正式对照试验的合理性。
Objective. To gain preliminary evidence for the safety and efficacy of B lymphocyte depletion therapy in refractory systemic lupus erythematosus (SLE).Methods. Six female patients with active SLE, resistant to standard immunosuppressive therapy, were treated on an open-label basis. During a 2-week period, each patient received two 500-mg infusions of rituximab, two 750-mg infusions of cyclophosphamide, and high-dose oral corticosteroids.Results. No significant adverse events were observed during followup. Patient 1 had not improved at 3 months but was then lost to followup. At 6 months, all 5 remaining patients had improved, as evidenced by improvement in British Isles Lupus Assessment Group global scores, from a median of 14 (range 9-27) at baseline to a median of 6 (range 3-8) at 6 months. Manifestations of SLE such as fatigue, arthralgia/arthritis, and serositis responded particularly well to this protocol. Hemoglobulin levels increased in patients 2, 3, 5, and 6. The erythrocyte sedimentation rate decreased in patients 2, 3, 4, and 5 and was stable in patient 1. In patients 4 and 5, the urinary protein-to-creatinine ratio decreased significantly. C3 serum levels increased in all 5 patients who had low levels at baseline; in two of these patients, patients 2 and 5, C3 values were normal at 6 months. The variation in the level of anti-double-stranded DNA antibody was different in individual patients.Conclusion. This study provides sufficient evidence for the safety and possible efficacy of B lymphocyte depletion therapy in SLE to justify a formal controlled trial.