托珠单抗治疗大动脉炎的疗效分析

The efficacy of tocflizumab on the treatment of Chinese Takayasu＇s arteritis

目的目的评价中国大动脉炎患者使用托珠单抗治疗的长期有效性和安全性。方法回顾性分析在2014年1月至2016年3月于北京协和医院使用托珠单抗治疗的18例活动期大动脉炎患者，记录其临床症状、实验室检查结果、血管影像学检查数据。计量资料采用t检验和秩和检验；计数资料采用Fisher精确或，检验。结果18例患者的中位年龄为25．5（18～47）岁。除1例初治患者因拒绝使用免疫抑制剂接受托珠单抗治疗外，余17例均为使用其他免疫抑制剂治疗中病情复发者，在接受托珠单抗治疗前使用的免疫抑制剂数目的中位数为3（1-5）种。3例患者在托珠单抗治疗1次后因难以耐受的颈部疼痛而停止托珠单抗治疗，其余15例患者使用托珠单抗的中位治疗时间为13（6～26）个月。15例患者经托珠单抗治疗后，ESR从45．5mm／1h降至7mm/1h（Z=6．731，P〈0．01），超敏CRP中位数从37．4mg/L降至0．94mg／L（Z=3．212，P=0．016），颈总动脉管壁厚度中位数从0．25cm降至0．18cm（Z=4．873，P=0．001），锁骨下动脉管厚度中位数从0．18cm降至0．12cm（Z=5．568，P〈0．01）。所有患者在治疗过程中糖皮质激素的使用剂量都有所降低。1例患者在托珠单抗治疗6个月后因无效停用。1例患者在治疗过程中出现尿路感染，使用抗生素后好转。无患者出现中性粒细胞减少（〈2．0×10^6L）及肝功能异常。结论长期使用托珠单抗治疗大动脉炎是有效、安全的，尤其是对于难治性患者。

Objective The aim of this study was to evaluate the long-term efficacy and safety of tocilizumab （TCZ） in Chinese patients with Takayasu＇s arteritis （TA）. Methods We retrospectively studied the active TA patients treated with TCZ from January 2014 to April 2016 in our hospital. The demographic and clinical data, laboratory tests and vascular images were collected. Doppler uhrasonography was used to track vascular changes during TCZ treatment. The data were analyzed by t test and rank sum test. The data were analyzed by Fisher exact test or Chi square test. Results Eighteen patients with a median age of 25.5 （range 18, 47） were analyzed. Seventeen patients had taken a median of 3 （range 1, 5） immune suppressants before TCZ therapy. Three patients withdrew TCZ after receiving 1 infusion each due to unbearable neck pain. The other 15 patients were treated with TCZ for a median of 13 （range 6, 26） months. After TCZ treatment, the median ESR level, hsCRP level, mural thickness of common carotid artery and subclavieal artery decreased from 45.5 （range 7-101） mm/1 h （Z=6.731, P〈0.01）, 37.40 （range 7.6-163.12） mg/L, 0.25 （range 0.06-0.59） cm, 0.18 （range 0.07-0.47） cm to 7 （range 1-44） mm/1 h （Z=6.731, P〈0.01）, 0.94 （range 0.08-93.21） mg/L （Z= 3.212, P=0.016）, 0.18 （range 0.04-0.53） cm （Z=4.873, P=0.001）, and 0.12 （range 0.07-0.18） em （Z=5.568, P〈 0.01） respectively, with median glucocorticoid dosage being successfully tapered. One patient discontinued TCZ for unsatisfactory response after 6 TCZ infusions. One episode of urinary infection was recorded and relieved after antibiotic therapy. Neither neutropenia nor abnormal liver enzyme was observed. Conclusion Our study suggests that tocilizumab is a safe and effective agent for long term use among Chinese TA patients, especially for those refractory cases.