B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients
B-cell depletion in the treatment of patients with systemic lupus erythematosus: a longitudinal analysis of 24 patients
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DOI：
10.1093/rheumatology/kei080
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发表时间：
2005-12-01
期刊：
影响因子：
5.5
通讯作者：
Isenberg, DA
中科院分区：
文献类型：
--
作者：
Leandro, MJ;Cambridge, G;Isenberg, DA
目标。旨在评估利妥昔单抗消除 B 细胞治疗常规免疫抑制失败的系统性红斑狼疮 (SLE) 患者的临床和基本血清学后果。方法。据报道，一项对 24 名严重 SLE 患者进行了至少 3 个月随访的开放研究。大多数患者（24 名患者中的 19 名）描述了 6 个月的随访数据。使用不列颠群岛狼疮评估组 (BILAG) 系统每 1-2 个月评估一次这些患者的疾病活动度，并估计抗双链 DNA 抗体和血清 C3 水平。在随访期间，发现了明显的副作用，并记录了口服泼尼松龙的减少。我们的一般做法是在进行 B 细胞清除时停止伴随的免疫抑制（例如硫唑嘌呤、麦考酚酯）（在大多数情况下，以间隔 2 周两次 1 g 利妥昔单抗静脉输注的形式，同时静脉输注两次 750 mg 环磷酰胺和两次每次 250 mg 甲泼尼龙输注）。结果。 22 名患者为女性，2 名男性。 B 细胞耗竭时，平均年龄为 28.9 岁（范围 17-49），平均病程为 7.9 岁（范围 1-18）。从 B 细胞去除时到治疗后 6 个月，总体 BILAG 评分（P < 0.00001）、血清 C3（P < 0.0005）和双链 DNA 结合（P < 0.002）均有所改善。只有一名患者未能实现外周血中 B 淋巴细胞的去除。 B 淋巴细胞清除期为 3 至 8 个月，只有一名患者的 B 淋巴细胞清除期超过 4 年。对定期 BILAG 评估的分析表明，八个器官或系统中的每一个都出现了改善。平均每日泼尼松龙剂量从 13.8 mg (s.d. 11.3) 降至 10 mg (s.d. 3.1)。结论。在这项对传统免疫抑制治疗失败的患者进行的开放性研究中，B 细胞消除的使用具有相当大的实用性。我们的数据为完整双盲对照试验的表现提供了强有力的支持。
Objectives. To assess the clinical and basic serological consequences of B-cell depletion with rituximab in the treatment of patients with systemic lupus erythematosus (SLE) who have failed conventional immunosuppression.Methods. An open study of 24 patients with severe SLE followed for a minimum of 3 months is reported. In the majority of patients (19 out of 24), 6 months follow-up data are described. Disease activity in these patients was assessed every 1-2 months using the British Isles Lupus Assessment Group (BILAG) system and estimates of anti-double-stranded DNA antibodies and serum C3 levels. During the follow-up period, significant side-effects were sought and the reduction in oral prednisolone was recorded. It was our general practice to stop concomitant immunosuppression (e.g. azathioprine, mycophenolate) when B-cell depletion was given (in most cases in the form of two 1 g intravenous infusions of rituximab 2 weeks apart accompanied by two 750 mg intravenous cyclophosphamide infusions and two methylprednisolone infusions of 250 mg each).Results. Twenty-two patients were female and two male. At the time of B-cell depletion, the mean age was 28.9 yr (range 17-49) and the mean disease duration was 7.9 yr (range 1-18). The global BILAG score (P < 0.00001), serum C3 (P < 0.0005) and double-stranded DNA binding (P < 0.002) all improved from the time of B-cell depletion to 6 months after this treatment. Only one patient failed to achieve B-lymphocyte depletion in the peripheral blood. The period of B-lymphocyte depletion ranged from 3 to 8 months except for one patient who remains depleted at more than 4 yr. Analysis of the regular BILAG assessments showed that improvements occurred in each of the eight organs or systems. The mean daily prednisolone dose fell from 13.8 mg (s.d. 11.3) to 10 mg (s.d. 3.1).Conclusion. In this open study of patients who had failed conventional immunosuppressive therapy, considerable utility in the use of B-cell depletion has been demonstrated. Our data provide strong support for the performance of a full double-blind control trial.