[Effectiveness and safety of rituximab for children with autoimmune diseases of the nervous system].

Objective: To assess the effectiveness and safety of rituximab in Chinese children with autoimmune diseases of the nervous system. Method: An ambispective cohort study enrolled patients with refractory and(or) relapse autoimmune diseases of nervous system from June 2010 to June 2016 in Peking University First Hospital.These patients failed to respond to steroids and(or)intravenous immunoglobulin (IVIG) were treated with rituximab and seen for follow-up visits once every 3 months.The effectiveness was assessed by modified Rankin scale (mRs) and the annualized relapse rate.B cell was repeatedly counted after the treatment.Side effects attributed to rituximab were recorded.Paired rank test and chi-square test were used to compare the mRs score and the recurrence rate (time/year) before and after the treatment. Result: A total of 38 patients (15 males and 23 females) with mean age of (6±4) years were treated with rituximab.Among those patients, 4 cases were in multiple sclerosis, 5 in neuromyelitis optica, 6 in opsoclonus myoclonus syndrome, 9 in myasthenia gravis, and 14 in autoimmune encephalitis and other nervous system autoimmune diseases.The course of the disease before rituximab treatment was from two months to 7.25 years, with the average of (21±19) months.The patients had been followed up for 2-52 months. The mRs score and recurrence rate of 38 patients before receiving rituximab was 3 points (3, 4) and 2.56 (1.80, 4.75) times per year, respectively, while patients after receiving rituximab were mRs score of 0 (0, 2) and had a recurrence rate of 0 (0, 0.17) per year.There was statistical difference before and after treatment (Z=-4.51 and -4.71, P<0.01). Rituximab had a definite benefit in 23 patients, probable benefit in 2 patients, possible benefit in 3 patients, no benefit in one patient, and the disease worsened in 2 patients.Therefore the total effective rate was 74%, except for 6 undetermined cases because of the short follow-up time, and one patient withdrew from the study due to allergic reaction.During the follow-up, only one patient with severe allergy gave up the rituximab treatment. And only one patient was found severe infection with Pneumocystis carinii pneumonia. Conclusion: Rituximab is an effective and safe treatment strategy for patients with refractory and relapse autoimmune diseases of CNS, especially in neuromyelitis optica and myasthenia gravis.The adverse events including infection and allergy during infusion are not common.目的： 评价利妥昔单抗在儿童神经系统自身免疫性疾病治疗中的效果及安全性。 方法： 采用双向性队列研究，对2010年6月至2016年6月于北京大学第一医院儿科诊断为神经系统自身免疫性疾病，经糖皮质激素或免疫球蛋白治疗无效或复发的住院患儿给予利妥昔单抗治疗，并每3个月随访1次，应用改良Rankin量表及年复发率进行疗效评价；行B细胞数值监测；观察药物的不良反应。采用配对秩和检验对每种疾病治疗前后应用改良Rankin量表评分及复发率(次/年)进行比较。 结果： 应用利妥昔单抗治疗的患儿共38例，其中男15例、女23例，平均年龄(6±4)岁，其中多发性硬化4例，视神经脊髓炎5例，眼球阵挛肌阵挛综合征6例，重症肌无力9例，免疫性脑炎及其他神经系统免疫性疾病14例。患儿病程2～87个月，平均(21±19)个月，随访时间2～52个月。38例患儿使用利妥昔单抗前改良Rankin量表评分3(3，4)分，年复发率2.56(1.8，4.75)次/年，使用利妥昔单抗后改良Rankin量表评分0(0，2)分，年复发率0(0，0.17)次/年，二者治疗前后差异均有统计学意义(Z＝－4.51、－4.71，P均<0.01)。38例患儿中控制23例，显效2例，有效3例，无效1例，加重2例，因随访时间短不能确定疗效6例，因过敏反应退出治疗1例，总有效率74%。出现严重的肺部卡氏肺囊虫感染1例。 结论： 利妥昔单抗治疗儿童难治性、复发性神经系统自身免疫性疾病尤其是视神经脊髓炎和重症肌无力安全性好，常见不良反应为过敏和感染。.