托珠单抗治疗重症和(或)难治性血管白塞病临床疗效  

Tocilizumab in the treatment of severe and/or refractory vasculo-Behcet's disease

作　　者：李超然 丁艳霞[2] 刘金晶 周佳鑫 田新平 曾小峰 张奉春 郑文洁 LI Chao-ran;DING Yan-xia;LIU Jin-jng;ZHOU Jia-xin;TIAN Xin-ping;ZENG Xiao-feng;ZHANG Feng-chun;ZHENG Wen-jie(Department of Rheumatology and Clinical Immunology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Key Laboratory of Rheumatology&Clinical Immunology,Ministry of Education,Beijing 100730,China;Department of Rheumatology and Clinical Immunology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 400052,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院风湿免疫科风湿免疫病学教育部重点实验室,北京100730 [2]郑州大学第一附属医院风湿免疫科,郑州450052

出　　处：《中华临床免疫和变态反应杂志》2019年第1期42-47,共6页Chinese Journal of Allergy & Clinical Immunology

基　　金：国家自然科学基金(81571598,81871299)。

摘　　要：目的探讨托珠单抗(tocilizumab,TCZ)治疗重症和(或)难治性血管白塞病(Behcet’s disease,BD)的疗效和安全性。方法回顾性分析北京协和医院2014年8月至2018年12月收治的15例接受TCZ治疗的血管性BD患者的临床资料。结果15例患者(包括14例男性和1例女性)平均年龄(36.6±9.0)岁,病程(109.1±57.3)个月。所有患者均有动脉受累,包括动脉瘤(n=10)、动脉狭窄(n=5)、大动脉扩张(n=4)和动脉闭塞(n=3),2例患者并发多发性静脉血栓。在TCZ治疗之前,14例患者经激素联合免疫抑制剂积极治疗后临床无明显改善,6例患者接受外科手术治疗后出现动脉瘤复发或瓣周漏等严重术后并发症。TCZ以8 mg/kg的剂量输注治疗,每4周1次,与中低剂量的皮质类固醇和免疫抑制剂联合使用,中位疗程为3(2~15)次。平均随访(13.4±9.2)个月后,所有患者的临床症状和血清炎症标志物都有所改善,且均未观察到新发动脉病变或静脉血栓形成。中位ESR[(18 vs.2)mm/h,P<0.05]和hsCRP水平[(21 vs.0.37)mg/L,P<0.05]也显著降低。中位泼尼松剂量从35(10~60)mg逐渐减少到12.5(5~50)mg(P<0.05),免疫抑制剂种类和剂量也减少。8例接受外科手术治疗的患者术后随访10(3~20)个月后情况稳定。未观察到严重感染或其他不良事件。结论TCZ与皮质类固醇和免疫抑制剂联合使用,对治疗严重和(或)难治性血管BD有效且耐受性良好,有利于类固醇和免疫抑制剂减量,有利于减少复发及术后并发症并改善预后。Objective To elucidate the efficacy and safety of Tocilizumab(TCZ)for severe and/or refractory vasculo-Behcet's disease(BD).Methods We retrospectively analyzed 15 vasculo-BD patients treated with TCZ in our center between 2014 and 2018.Results 15 patients(14 males and 1 female)were enrolled,with a mean age of(36.6±9.0)years old and mean course of(109.1±57.3)months.Multiple arterial lesions were documented in all patients,including arterial aneurysm(n=10),stenosis(n=5),dilation(n=4),and occlusion(n=3),and multiple venous thrombosis were documented in two patients.Prior to TCZ therapy,14 patients had failed to high-dose glucocorticoid in combination with multiple immunosuppressants.Six patients underwent 7 surgeries and serious complications such as recurrence of aneurysm or perivalvular leakage were observed.TCZ was administrated at 8 mg/kg iv every 4 weeks for a median of 3 times,in combination with low-to-medium-dose corticosteroids and immunosuppressants.After a mean follow-up of(13.4±9.2)months,all the patients achieved both clinical and serological improvements.No newly-onset arterial lesions or venous thrombosis were observed.The median ESR[(18 vs.2)mm/h,P<0.05]and hsCRP level[(21 vs.0.37)mg/L,P<0.05]were also significantly decreased.Furthermore,the median dosage of corticosteroids was tapered from 35(10-60)mg to 12.5(5-50)mg(P<0.05),and immunosuppressants were also tapered in number and dosage.Eight patients receiving surgical treatment subsequently were stable after a median postoperative follow-up of 10(3-20)months.No serious adverse events or TB reactivation were observed.Conclusion TCZ,in combination with corticosteroids and immunosuppressants,was effective and well tolerated in severe and/or refractory vasculo-BD,with a favorable steroid-and immunosuppressant-sparing effect.

关 键 词：白塞病 血管受累 托珠单抗 

分 类 号：R73[医药卫生—肿瘤]