抗肿瘤坏死因子α单抗治疗16例重症/难治性血管白塞病的疗效与安全性  

Efficacy and safety of anti-tumor necrosis factorαmonoclonal antibodies in 16 patients with severe/refractory vasculo Behcet's disease

作　　者：李璐 刘金晶 郁欣 吴迪 张上珠 杨云娇 周佳鑫 曾小峰 张奉春 郑文洁 Li Lu;Liu Jinjing;Yu Xin;Wu Di;Zhang Shangzhu;Yang Yunjiao;Zhou Jiaxin;Zeng Xiaofeng;Zhang Fengchun;Zheng Wenjie(Department of Rheumatology and Clinical Immunology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Key Laboratory of Rheumatology&Clinical Immunology,Ministry of Education,Peking Union Medical College Hospital Translational Medical Center,National Clinical Research Center for Dermatologic and Immunologic Diseases,Beijing 100730,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,协和转化医学中心,国家皮肤与免疫疾病临床医学研究中心,100730

出　　处：《中华内科杂志》2020年第4期303-308,共6页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金(81871299)。

摘　　要：目的:初步探讨抗肿瘤坏死因子α(TNFα)单抗治疗重症/难治性血管白塞病的疗效与安全性。方法:回顾性分析16例应用抗TNFα单抗治疗的重症/难治性血管白塞病患者的临床资料及抗TNFα单抗的疗效,比较联合用药前后糖皮质激素剂量、红细胞沉降率(ESR)和超敏C反应蛋白(CRP)水平,记录不良反应。结果:16例血管白塞病患者男性14例,女性2例,年龄(35.8±13.7)岁,病程(10.5±5.8)年。白塞病起病至出现血管病变(7.5±5.3)年,16例患者中动脉系统受累12例,表现为动脉瘤(9例)、动脉扩张(6例)、动脉狭窄(2例)和动脉闭塞(2例);静脉血栓7例,受累部位包括下肢静脉(6例)、下腔静脉(2例)和颅内静脉窦(2例);动静脉系统均有受累者2例。应用抗TNFα单抗前,16例患者经泼尼松或等效剂量糖皮质激素40(7.5~90)mg/d联合环磷酰胺、甲氨蝶呤、沙利度胺、硫唑嘌呤等免疫抑制剂中位治疗4(0~156)个月后疗效不佳。联合应用英夫利西单抗3~5 mg/kg或阿达木单抗40mg/次,平均疗程(17.1±6.5)个月后,15例患者达到完全缓解,1例患者达到部分缓解。3例患者行外科手术治疗,均未发生术后并发症。治疗后,泼尼松剂量[5(0~12.5)mg/d比40(7.5~90)mg/d,P<0.01]、ESR[(7.3±4.6)mm/1h比(33.5±26.7)mm/1h,P<0.01]、超敏CRP[1.9(0.2~11.4)mg/L比24.3(0.4~113.9)mg/L,P<0.01]较治疗前显著下降。2例患者出现不良反应,1例应用阿达木单抗联合传统治疗12个月后出现肺部感染,停用阿达木单抗并给予抗感染治疗后好转;1例首次应用英夫利西单抗过程中,出现过敏反应,之后换用阿达木单抗后无过敏反应发生。结论:对重症/难治性血管白塞病,应用抗TNFα单抗与糖皮质激素和免疫抑制剂联合治疗,有效且耐受性好,有利于减少糖皮质激素用量及术后并发症。Objective To explore the efficacy and safety of anti-tumor necrosis factor alpha(TNFα)monoclonal antibodies(mAbs)for severe/refractory vasculo-Behcet's disease(BD).Method The clinical data of severe/refractory vasculo-BD patients treated with anti-TNFαmAbs were retrospectively analyzed.Response of anti TNFαmAbs was analyzed.The dosage changes of glucocorticoid,the level of erythrocyte sedimentation rate(ESR)and hypersensitive C-reactive protein(hsCRP)before and after treatment were recorded,as well as side effects.Result Sixteen patients were enrolled.Arterial lesions were reported in 12 patients,including 9 with arterial aneurysm,6 with arterial dilation,2 with stenosis and 2 with occlusion.Seven patients presented venous thrombosis,including lower extremity veins(n=6),cerebral venous sinus(n=2)and inferior vena cava system(n=2).Two cases had both arterial and venous involvement.Before the application of TNFαmAbs,all 16 patients failed to response to prednisone or its equivalent dose of 40(7.5-90)mg/d in combination with cyclophosphamide,methotrexate,thalidomide or azathioprine for median 4(0-156)months.After a mean duration of treatment for(17.1±6.5)months,15 patients achieved complete remission and 1 patient achieved partial remission.Three patients received surgery without any postoperative complications.After using anti TNFαmAbs,the dosage of prednisone[5(0-12.5)mg/d vs.40(7.5-90)mg/d,P<0.01],ESR[(7.3±4.6)mm/1h vs.(33.5±26.7)mm/1h,P<0.01]and hsCRP[1.9(0.2-11.4)mg/L vs.24.3(0.4-113.9)mg/L,P<0.01]were significantly decreased.Side effects were observed in 2 patients.One developed pulmonary infection 12 months after adalimumab with conventional treatment.Another patient had allergy to infliximab then switched to adalimumab.Conclusion In combination with corticosteroids and immunosuppressants,anti-TNFαmAbs are effective and well-tolerated in severe/refractory vasculo-BD,with a favorable steroid-sparing effect and rare postoperative complications.

关 键 词：贝赫切特综合征 血管受累 抗肿瘤坏死因子单抗 疗效 安全性 

分 类 号：R5[医药卫生—内科学]