Low-dose rituximab therapy for refractory thrombocytopenia in patients with systemic lupus erythematosus-a prospective pilot study
Low-dose rituximab therapy for refractory thrombocytopenia in patients with systemic lupus erythematosus-a prospective pilot study
复制标题
小剂量利妥昔单抗治疗系统性红斑狼疮难治性血小板减少症的前瞻性先导研究
DOI：
10.1093/rheumatology/ker176
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发表时间：
2011-09-01
期刊：
影响因子：
5.5
通讯作者：
Zhang, Fengchun
中科院分区：
文献类型：
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作者：
Chen, Hua;Zheng, Wenjie;Zhang, Fengchun
目标.评价小剂量利妥昔单抗治疗SLE患者难治性血小板减少症的安全性和有效性。10例患有严重难治性血小板减少症（平均血小板计数10.4 × 10（9）/l）的成人SLE患者入选本前瞻性初步研究。所有患者都失败了传统的高剂量CS和免疫抑制剂，包括甲基强的松龙脉冲治疗。患者计划接受静脉注射利妥昔单抗，剂量为100 mg，每周一次，持续4周。既往剂量的CS逐渐减量，并停用免疫抑制剂。在第4、12、24和36周对患者进行随访。所有患者均完成4个疗程的低剂量利妥昔单抗输注。在第4周，2例（20%）患者达到完全缓解（CR，血小板计数> 100 x 10（9）/l）。CR率在第12周增加至60%（6例患者），在第24周维持，并在第36周开始下降（4例患者，40%）。在第4、12、24和36周，分别有5/10、6/10、7/10和5/10例患者达到总体缓解（OR，血小板计数> 50 x 10（9）/l）。在第4周时，所有患者的外周血CD 19（+）B细胞均被清除（< 5 x 10（6）/l），并在第24周和第36周时逐渐增加。血清C3、IgG、伊加、IgM水平无明显变化（P> 0.05）。2例患者出现输液反应。1例患者在第14周发生肺血栓形成，在第25周发生活动性结核。低剂量利妥昔单抗治疗对强糖皮质激素联合免疫抑制剂无效的SLE患者的严重血小板减少症是有效的，并且在大多数情况下是安全的。
Objectives. To evaluate the safety and efficacy of low-dose rituximab therapy for refractory thrombocytopenia in patients with SLE.Methods. Ten adult SLE patients with severe refractory thrombocytopenia (mean platelet count 10.4 x 10(9)/l) were enrolled in this prospective pilot study. All patients had failed traditional high-dose CSs and immunosuppressants including methylprednisolone pulse therapy. Patients were scheduled to receive i.v. rituximab at a dose of 100 mg once weekly for 4 weeks. Previous dose of CSs were gradually tapered, and immunosuppressants were withdrawn. Patients were followed at Weeks 4, 12, 24 and 36.Results. All patients completed four courses of low-dose rituximab infusion. At Week 4, two (20%) patients achieved complete responses (CRs, platelet count > 100 x 10(9)/l). The CR rate increased to 60% (six patients) at Week 12, was maintained at Week 24 and began to drop at Week 36 (four patients, 40%). Overall response (OR, platelet count > 50 x 10(9)/l) was achieved in 5/10, 6/10, 7/10 and 5/10 patients at Weeks 4, 12, 24 and 36, respectively. Peripheral CD19(+) B cells were depleted (< 5 x 10(6)/l) in all patients at Week 4, and gradually increased at Weeks 24 and 36. Serum C3, IgG, IgA and IgM levels did not change significantly (P < 0.05). Infusion reaction was observed in two patients. One patient developed pulmonary thrombosis at Week 14 and active tuberculosis at Week 25.Conclusions. Low-dose rituximab therapy is effective in treating severe thrombocytopenia in SLE patients who do not respond to vigorous glucocorticoid plus immunosuppressants, and in most cases is safe.