Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study
Treatment of neuromyelitis optica with rituximab: a 2-year prospective multicenter study
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DOI：
10.1007/s00415-018-8771-5
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发表时间：
2018-04-01
影响因子：
6
通讯作者：
Marignier, R.
中科院分区：
文献类型：
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作者：
Cabre, Philippe;Mejdoubi, M.;Marignier, R.
视神经脊髓炎(NMO)是一种严重的中枢神经系统自身免疫性疾病。它影响年轻的受试者，在功能和生命水平上预后都很差。因此，减少复发的频率势在必行。本研究的目的是评价利妥昔单抗(RTX)治疗活动性NMO的临床和神经放射学疗效。我们进行了一项为期2年的多中心开放前瞻性研究，32例患者接受RTX治疗，剂量为375 mg/m(2)/周，疗程为1个月。当循环中CD19+B细胞的数量达到1%时，开始维持治疗，包括两次输注1g的RTX，间隔15天。主要目标是降低年复发率(ARR)，与治疗前两年观察到的相比，利妥昔单抗治疗将ARR从1.34%降低到0.56%(p=0.0005)。两年后扩展残疾状态量表(EDSS)平均评分由5.9(2~9)分提高到4.8(0~9)分，平均提高1.1分(p=0.03)。抗水通道蛋白-4抗体水平预示治疗失败(p=0.03)。脊髓Gad+病变的发生率由23.3%降至14.2%。RTX治疗未能阻止3名患者的死亡(2名患者治疗失败，1名曾接受米托蒽酮治疗的患者死于急性髓系白血病)。Rituximab对活动型NMO临床有效，尽管很少有患者对该治疗产生抗药性。
Neuromyelitis optica (NMO) is a very severe autoimmune disorder of the central nervous system. It affects young subjects and has a poor prognosis both on a functional and vital level. Therefore, it is imperative to reduce the frequency of relapses. The purpose of this study was to evaluate the clinical and neuroradiological effectiveness of rituximab (RTX) on active forms of NMO.We conducted a 2-year open prospective multicenter study that included 32 patients treated with RTX at a dose of 375 mg/m(2)/week for 1 month. When the number of circulating CD19+ B cells reached 1%, a maintenance therapy was started, consisting of two infusions of 1 g of RTX, administered at a 15-day interval. The primary objective was to reduce the annual relapse rate (ARR), in comparison to that observed in the 2 years before treatment onset.Rituximab administration reduced the ARR from 1.34 to 0.56 (p = 0.0005). The average Expanded Disability Status Scale (EDSS) score significantly improved by 1.1 point, from 5.9 (2-9) to 4.8 (0-9) after 2 years (p = 0.03). Anti-aquaporin-4 antibodies' level predicted treatment failure (p = 0.03). Frequency of Gad+ lesions in spinal cord decreased from 23.3 to 14.2%. RTX treatment did not prevent the death of three patients (treatment failure in two patients and acute myeloid leukemia in a patient previously treated with mitoxantrone).Rituximab is clinically effective in active forms of NMO, although few patients are resistant to the treatment.