Leandro M J, Cambridge G, Edwards J C, Ehrenstein M R, Isenberg D A
Centre for Rheumatology, University College London, London, UK.
Rheumatology (Oxford). 2005 Dec;44(12):1542-5. doi: 10.1093/rheumatology/kei080. Epub 2005 Sep 27.
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.
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).
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).
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.
评估利妥昔单抗清除B细胞在治疗常规免疫抑制治疗无效的系统性红斑狼疮（SLE）患者中的临床和基础血清学后果。
报告了一项对24例重症SLE患者进行的开放性研究，随访至少3个月。在大多数患者（24例中的19例）中，描述了6个月的随访数据。使用不列颠群岛狼疮评估组（BILAG）系统以及抗双链DNA抗体和血清C3水平的估计值，每1 - 2个月评估一次这些患者的疾病活动度。在随访期间，寻找显著的副作用并记录口服泼尼松龙的减量情况。我们的常规做法是在给予B细胞清除治疗时（大多数情况下为间隔2周静脉输注两次1 g利妥昔单抗，同时静脉输注两次750 mg环磷酰胺和两次各250 mg甲泼尼龙）停止同时使用的免疫抑制药物（如硫唑嘌呤、霉酚酸酯）。
22例为女性，2例为男性。在进行B细胞清除治疗时，平均年龄为28.9岁（范围17 - 49岁），平均病程为7.9年（范围1 - 18年）。从B细胞清除治疗时到治疗后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。仅1例患者外周血未实现B淋巴细胞清除。除1例患者在4年多后仍处于淋巴细胞清除状态外，B淋巴细胞清除期为3至8个月。对定期BILAG评估的分析表明，八个器官或系统中的每一个都有改善。泼尼松龙的日均剂量从13.8 mg（标准差11.3）降至10 mg（标准差3.1）。
在这项对常规免疫抑制治疗无效患者的开放性研究中，已证明使用B细胞清除疗法具有相当大的效用。我们的数据为进行全面的双盲对照试验提供了有力支持。
