Dalakas Marinos C, Rakocevic Goran, Salajegheh Mohammad, Dambrosia James M, Hahn Angelika F, Raju Raghavan, McElroy Beverly
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Ann Neurol. 2009 Mar;65(3):286-93. doi: 10.1002/ana.21577.
Report a double-blind, placebo-controlled study of rituximab in patients with anti-MAG demyelinating polyneuropathy (A-MAG-DP).
Twenty-six patients were randomized to four weekly infusions of 375 mg/m(2) rituximab or placebo. Sample size was calculated to detect changes of > or = 1 Inflammatory Neuropathy Course and Treatment (INCAT) leg disability scores at month 8. IgM levels, anti-MAG titers, B cells, antigen-presenting cells, and immunoregulatory T cells were monitored every 2 months.
Thirteen A-MAG-DP patients were randomized to rituximab and 13 to placebo. Randomization was balanced for age, electrophysiology, disease duration, disability scores, and baseline B cells. After 8 months, by intention to treat, 4 of 13 rituximab-treated patients improved by > or = 1 INCAT score compared with 0 of 13 patients taking placebo (p = 0.096). Excluding one rituximab-randomized patient who had normal INCAT score at entry, and thus could not improve, the results were significant (p = 0.036). The time to 10m walk was significantly reduced in the rituximab group (p = 0.042) (intention to treat). Clinically, walking improved in 7 of 13 rituximab-treated patients. At month 8, IgM was reduced by 34% and anti-MAG titers by 50%. CD25+CD4+Foxp3+ regulatory cells significantly increased by month 8. The most improved patients were those with high anti-MAG titers and most severe sensory deficits at baseline.
Rituximab is the first drug that improves some patients with A-MAG-DP in a controlled study. The benefit may be exerted by reducing the putative pathogenic antibodies or by inducing immunoregulatory T cells. The results warrant confirmation with a larger trial.
报告一项关于利妥昔单抗治疗抗MAG脱髓鞘性多发性神经病（A-MAG-DP）患者的双盲、安慰剂对照研究。
26例患者被随机分为接受4次每周一次的375mg/m²利妥昔单抗或安慰剂静脉输注。计算样本量以检测第8个月时炎症性神经病病程和治疗（INCAT）腿部残疾评分变化≥1分。每2个月监测IgM水平、抗MAG滴度、B细胞、抗原呈递细胞和免疫调节性T细胞。
13例A-MAG-DP患者被随机分配接受利妥昔单抗治疗，13例接受安慰剂治疗。随机分组在年龄、电生理、疾病持续时间、残疾评分和基线B细胞方面是均衡的。8个月后，按意向性分析，13例接受利妥昔单抗治疗的患者中有4例INCAT评分改善≥1分，而13例接受安慰剂治疗的患者中无1例改善（p = 0.096）。排除1例入组时INCAT评分正常因而无法改善的随机接受利妥昔单抗治疗的患者后，结果具有显著性（p = 0.036）。利妥昔单抗组10米步行时间显著缩短（p = 0.042）（意向性分析）。临床上，13例接受利妥昔单抗治疗的患者中有7例步行能力改善。在第8个月时，IgM降低了34%，抗MAG滴度降低了50%。到第8个月时，CD25+CD4+Foxp3+调节性细胞显著增加。改善最明显的患者是那些基线时抗MAG滴度高且感觉障碍最严重的患者。
在一项对照研究中，利妥昔单抗是首个使部分A-MAG-DP患者病情改善的药物。其益处可能是通过减少假定的致病抗体或诱导免疫调节性T细胞来实现的。这些结果有待更大规模试验的证实。
