Use and monitoring of low dose rituximab in myasthenia gravis
Use and monitoring of low dose rituximab in myasthenia gravis
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DOI：
10.1136/jnnp.2010.220475
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发表时间：
2011-06-01
影响因子：
11
通讯作者：
Wong, Richard
中科院分区：
文献类型：
--
作者：
Blum, Stefan;Gillis, David;Wong, Richard
背景重症肌无力是一种发生于神经肌肉接头处的自身免疫性疾病。利妥昔单抗（Rituximab，RTX）是一种抗CD20单克隆抗体，可导致B淋巴细胞耗竭，已被用于治疗一些自身免疫性疾病，包括重症肌无力患者的小病例系列。（11例受试者）或肌肉特异性激酶抗体（MuSK）阳性重症肌无力（3例受试者），他们在澳大利亚布里斯班接受过RTX治疗。在大多数患者中，给予1 g RTX，分两次给药。通过一系列临床评估、外周血B淋巴细胞流式细胞术和抗体检测对患者进行监测。14名患者中有12名能够减少免疫抑制药物的剂量，但只有1名患者可以完全停止药物治疗。一个可证明的自身抗体水平的降低，发现只有三个AChR阳性患者和一个MuSK阳性患者，独立的临床改善。14例患者中有13例达到外周血B淋巴细胞耗竭。B淋巴细胞的恢复发生在9和30个月后RTX（中位数12.3个月），并始终与临床症状恶化。结论利妥昔单抗在1 g的剂量似乎是有益的重症肌无力患者的治疗。外周血B淋巴细胞的系列监测似乎有助于指导进一步RTX治疗的需要。
Background Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Rituximab (RTX), a monoclonal antibody to CD20, leads to B lymphocyte depletion and has been used in some autoimmune disorders, including small case series of myasthenia gravis patients.Methods A retrospective analysis was performed of all patients with acetylcholine receptor (AChR) (11 subjects) or muscle specific kinase antibody (MuSK) positive myasthenia gravis (three subjects), who had been treated with RTX in Brisbane, Australia. In most patients 1 g of RTX, in two divided doses, was given. Patients were monitored by serial clinical assessments, flow cytometry of peripheral blood B lymphocytes and antibody testing.Results RTX led to a significant improvement in symptoms in 11 of 14 patients. Doses of immunosuppressive medications were able to be reduced in 12 of 14 patients but medications could be completely ceased in only one patient. A demonstrable reduction of autoantibody levels was found in only three AChR positive patients and one MuSK positive patient, independent of clinical improvement. Peripheral blood B lymphocyte depletion was achieved in 13 out of 14 patients. B lymphocyte recovery occurred between 9 and 30 months post RTX (median 12.3 months) and was consistently associated with worsening of clinical symptoms.Conclusion Rituximab at a dose of 1 g appears to be beneficial in the treatment of patients with severe myasthenia gravis. Serial monitoring of peripheral blood B lymphocytes appears to be useful in guiding the need for further RTX therapy.