小剂量利妥昔单抗预防视神经脊髓炎谱系疾病复发的有效性及安全性研究  

Efficacy and safety of low-dose rituximab in preventing neuromyelitis optica spectrum disorder relapse

作　　者：孙明明 周欢粉[1] 赵杰 张磊[1] 张媛[3] 宋宏鲁 白文浩 徐歆桐 张倩[1] 梁乾惠 王学敏 魏世辉[1] 徐全刚[1] SUN Mingming;ZHOU Huanfen;ZHAO Jie;ZHANG Lei;ZHANG Yuan;SONG Honglu;BAI Wenhao;XUXintong;ZHANG Qian;LIANG Qianhui;WANG Xuemin;WEI Shihui;XU Quangang(The Third Medical Center of PLA General Hospital&Chinese PLA Medical School,Beijing 100069;Beijing MEM Ding Hui Medical,Beijing 100142;The First Medical Center of PLA General Hospital&Chinese PLA Medical School,Beijing 100853;The Medical School of Chinese People’s Liberation Army(PLA),Beijing 100853,China)

机构地区：[1]解放军总医院第三医学中心,北京100039 [2]北京美尔目定慧医院,北京100142 [3]解放军总医院第一医学中心,北京100853 [4]解放军医学院研究生院,北京100853

出　　处：《眼科学报》2023年第3期199-205,共7页Eye Science

基　　金：中国博士后科学基金(2019M653944)。

摘　　要：目的:探讨小剂量利妥昔单抗(rituximab,RTX)预防视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder,NMOSD)复发的有效性和安全性。方法:采用前瞻性自身对照试验,选取2020年7月至2021年4月临床确诊为NMOSD的38例患者进行研究,给予小剂量RTX治疗。所有患者均进行病史采集、眼科检查和血清学指标检测,记录NMOSD年复发率(ARR)、最佳矫正视力(BCVA)、合并自身抗体情况和追加治疗的情况。视力检查采用Snellen视力表进行,并将结果转换为最小分辨角对数(log MAR)视力记录。随访至少12个月(17.29±2.2)个月,以末次随访为疗效判定时间点,比较治疗前后ARR、BCVA;分析复发与发病年龄、是否合并自身免疫抗体阳性和患自身免疫性疾病的关系。记录不良反应的发生率和追加治疗的时间。结果:共38例患者61眼纳入研究。其中男性4例,女性34例。发病年龄12~60岁,中位发病年龄23 (18~29.3)岁。病程10.0~265个月,中位病程65 (48.3~101.0)个月。治疗前log MAR矫正视力(1.15±0.13),治疗后log MAR矫正视力(1.54±0.39),比较差异无统计学意义(t=1.120,P=0.267)。治疗前ARR(1.50±0.86)次/年,治疗后ARR降低为(0.12±0.07)次/年,比较差异有统计学意义(t=8.304,P<0.001)。追加治疗时间为(6.4±2.3)月。随访期间3例患者复发,复发次数为5次。复发者与未复发者的发病年龄、合并免疫抗体阳性比例、合并自身免疫性疾病比例比较,差异均无统计学意义(均P>0.05)。38例患者中,出现输注不良反应7例,给予减慢RTX滴速及加用地塞米松5 mg治疗后均缓解,随访期间未见其他明显不良反应。结论:小剂量RTX可以有效清除B淋巴细胞,预防NMOSD复发,且安全性较好。Objective:To evaluate the efficacy and safety of low-dose rituximab(RTX)in preventing neuromyelitis optica spectrum disorders(NMOSD).Methods:A prospective self-control trial was used to select a total of 38 patients clinically diagnosed as NMOSD from July 2020 to April 2021 for the study,and low-dose RTX was given for treatment.All patients underwent medical history,ophthalmic examination and serological test to record the annual recurrence rate(ARR),best corrected visual acuity(BCVA),combined autoantibodies and adjuvant therapy status.The BCVA was examined using Snellen eye chart,and the results were converted to logarithm of minimal angle resolution(logMAR).The patients were followed up for at least 12(17.29±2.2)months,and the last follow-up was taken as the time point of efficacy evaluation.The ARR and BCVA before and after treatment were compared.The relationship between relapse and age of onset,positivity for combination of autoimmune antibodies and autoimmune diseases was analyzed.The incidence of side effects and duration of additional therapy were recorded.Results:A total of 38 NMOSD patients(4 male/34 female,61 involved eyes)were included in this study.The ages of onset was 12-60 years old,the median onset age was 23(18-29.3)years.Duration of disease was 10-265 months,the median duration was 65(48.3-101.0)months.Before treatment,the mean logMAR BCVA was(1.15±0.13),the mean logMAR BCVA after treatment was(1.54±0.39),showing no significant difference(t=1.120,P=0.267).The mean ARR before and after treatment were(1.50±0.86)and(0.12±0.07),respectively,with significant difference(t=8.304,P<0.001).The duration of additional treatment was(6.4±2.3)months.Five relapses in three patients were observed.There was no significant difference between on onset ages of relapsed patients and non-relapsed patients,the proportion of auto-immune antibody,and the proportion of auto-immune diseases(all P>0.05).Among 38 patients,7 patients had side effects of infusion,which were relieved after slowing down the infusion spee

关 键 词：视神经脊髓炎谱系疾病 水通道蛋白4 利妥昔单抗 复发 

分 类 号：R744.52[医药卫生—神经病学与精神病学]