摘要
目的 观察小剂量利妥昔单抗（RTX）预防视神经脊髓炎谱系疾病（NMOSD）复发的有效性和安全性。 方法 前瞻性自身对照试验。临床确诊为NMOSD且病程超过1年的21例患者纳入研究。其中，男性1例，女性20例。发病年龄10～51岁，平均发病年龄（26.2±12.3）岁。病程2.3～25.8年，平均病程（9.2±5.9）年。所有患者均进行病史采集、眼科检查、血清学检验及神经系统查体，记录其NMOSD的年复发率（ARR）、矫正视力及扩展残疾状态量表（EDSS）评分。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（logMAR）视力记录。患者平均logMAR矫正视力1.13±1.09；最佳眼平均logMAR矫正视力0.40±0.68，最差眼平均logMAR矫正视力1.87±0.90。平均EDSS（3.09±0.70）分。平均ARR（1.04±0.65）次/年。所有患者均完成两周期的RTX诱导治疗。RTX 100 mg/次，50 mg/h速率滴注，每周1次，连用4周。1年1次诱导治疗，共2次。其中，发病1个月内立即接受诱导治疗12例，发病1个月后缓解期接受诱导治疗9例。治疗后平均随访时间（28.4±4.9）个月。观察治疗后不良反应的发生情况。以末次随访为疗效判定时间点；采用配对t检验对比分析治疗前后患者的矫正视力、ARR及EDSS评分；采用独立样本t检验对复发者与未复发者发病年龄进行两两比较；采用χ2检验对复发者与未复发者是否经血浆置换治疗以及合并免疫抗体阳性或患自身免疫性疾病比例等进行统计分析。 结果 治疗后患者平均logMAR矫正视力0.62±0.91；最佳眼平均logMAR矫正视力0.24±0.59，最差眼平均logMAR矫正视力1.00±1.01。平均EDSS评分（2.26±1.07）分。平均ARR（0.21±0.3）次/年。与治疗前比较，治疗后最差眼平均矫正视力明显提高（t=4.256），平均EDSS评分（t=4.620）、ARR（t=2.900）降低，差异均有统计学意义（P＜0.05）。治疗前后最佳眼平均矫正视力比较，差异无统计学意义（t=1.840，P＞0.05）。随访期间9例患者复发，复发次数为13次。13次复发中，B淋巴细胞检验12次，B淋巴细胞百分比为0.01%～0.14%。复发者与未复发者的发病年龄（t=0.67）、是否经血浆置换治疗（χ^2=1.61）、合并免疫抗体阳性或患自身免疫性疾病比例（χ^2=1.61）比较，差异均无统计学意义（P＞0.05）。21例患者中，出现不良反应8例。其中，继发感染5例，胸闷4例，脱发3例，皮疹、头痛、呼吸困难各2例，耳鸣、心慌、疲倦嗜睡各1例。合并两种及以上不良反应4例。对于出现不良反应者，给予减慢RTX滴速及加用地塞米松5 mg后缓解。 结论 小剂量RTX治疗NMOSD可降低ARR，安全性较好。
Objective To evaluate the efficacy and safety of repeated treatments with low-dose rituximab for relapsing neuromyelitis optica spectrum disorder （NMOSD）. Methods A perspective study. 21 patients who were diagnosed with NMOSD one year ago were recruited for rituximab treatment. Of 21 patients, one was male, 20 were females. Onset age was 10 - 51 years, the mean onset age was （26.2±12.0） years. Duration of disease was 2.3 - 25.8 years, the mean duration was （9.2±5.9） years. Best corrected vision activity （BCVA）, expanded disability status scale （EDSS）, annualized relapsing rate （ARR） were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. The BCVA was examined using Snellen chart, and converted to logMAR. The mean BCVA was 1.13±1.09, the mean BCVA in better eyes was 0.4±0.68, the mean BCVA in latter eyes was 1.87±0.90. The mean EDSS was 3.09±0.70. The mean ARR was 1.04±0.65. All patients underwent two cycles of RTX treatment. The annually induction treatment was RTX 100 mg per week for 4 weeks. Of 21 patients, 12 patients had treatment within one month after attack. The mean follow-up period was （28.4±4.9） months. The side effects were recorded, BCVA, EDSS, ARR were valued to investigate the efficacy and safety of repeated treatments with low-dose rituximab. Paired t test, independent sample t test and Chi-squared test were used. Results The mean BCVA at last follow-up was 0.62±0.91, the mean BCVA in better eye was 0.62±0.91, the BCVA in latter eye was 1.0±1.01. The mean EDSS was 2.26±1.07. The mean ARR was 0.21 ± 0.3. After the treatment, patient had significant improvement on BCVA in worst eye （t=4.256）, ARR （t=2.900）, EDSS （t=4.620） with the significant differences （P〈0.05）.Thirteen relapses in 9 patients were observed. B lymph cells were more than 0.01% in all relapses. There was no significant difference on the BCVA in better eye （t=1.840, P〉0.05）. There were 9 patients had relapse, 13 times in total. Of 13 relapses, B lymph cell count was performed in 12 relapses, and the counts were 0.01% - 0.14%. There were no significant difference between relapsed patients and non-relapsed patients on onset age （t=0.67, P=0.51）, whether underwent plasma exchange treatment （χ^2=1.61, P〉0.05）, with/without auto-immune antibody ratio （χ^2=1.61, P〉0.05）. Of 21 patients, 8 patients had side effects, including 5 patients with infection, 4 patients with chest congestion, 3 patients with hair losing, 2 patients with skin rashes, headache and short of breath, 1 patient with tinnitus, palpitation and fatigue. Four patients had more than one symptom. Of all patients who had side effects, slowing down the infusion speed of RTX or infusing 5 mg of dexamethasone could relieve the discomfort. Conclusion Lose-dose rituximab reduces the frequency of NMOSD relapses and is well tolerated.
出处
《中华眼底病杂志》
CAS
CSCD
北大核心
2018年第2期155-158,共4页
Chinese Journal of Ocular Fundus Diseases
