戈利木单抗治疗白塞综合征心脏大血管受累的临床分析  

Clinical analysis of golimumab in the treatment of severe/refractory cardiovascular involvement in Behcet syndrome

作　　者：孙鹿希 刘金晶 侯云霞[2] 李超然 李璐 田新平 曾小峰 郑文洁 SUN Lu-xi;LIU Jin-jing;HOU Yun-xia;LI Chao-ran;LI Lu;TIAN Xin-ping;ZENG Xiao-feng;ZHENG Wen-jie(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, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing 100730, China;Department of Rheumatology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, 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,北京100730 [2]内蒙古医科大学附属医院风湿免疫科,呼和浩特010050

出　　处：《北京大学学报（医学版）》2020年第6期1056-1062,共7页Journal of Peking University:Health Sciences

基　　金：国家自然科学基金(81871299)。

摘　　要：目的:探索戈利木单抗(golimumab,GOL)治疗重症/难治性心脏大血管白塞综合征(Behcet syndrome,BS)的疗效和安全性。方法:分析北京协和医院2018年2月—2020年7月使用GOL治疗的9例重症/难治性BS大血管和心脏瓣膜受累患者的临床资料,记录治疗前后红细胞沉降率(erythrocyte sedimentation rate,ESR)、超敏C反应蛋白(high-sensitivity C-reactive protein,hsCRP)水平、临床症状和影像学变化、合并用药的种类和剂量。结果:9例患者中男性8例、女性1例,平均年龄(37.0±8.6)岁,中位病程120(60,132)个月。患者中重度主动脉瓣关闭不全7例,多发动脉瘤、静脉血栓2例。7例患者既往应用激素联合免疫抑制剂/调节剂治疗,仍出现大血管病变进展或围手术期炎症指标明显升高;5例患者病情进展,需短期内手术治疗;3例患者新近完成心脏手术但既往反复出现严重术后并发症或术前炎症未控制;1例应用托珠单抗,新发消化道溃疡,需调整用药。患者应用GOL(50 mg,每4周皮下注射一次)与糖皮质激素和免疫抑制剂/调节剂联合治疗,随访(16.3±5.6)个月,临床症状均有改善,无新发大血管病变。8例患者行手术治疗,均未出现术后并发症。治疗后炎症指标下降,ESR由16.5(6.8,52.5)mm/h降至4(2,7)mm/h,hsCRP由21.24(0.93,32.51)mg/L降至0.58(0.37,1.79)mg/L(P<0.05)。泼尼松剂量由35(15,60)mg/d减至10.0(10.0,12.5)mg/d,环磷酰胺剂量均减量,6例患者GOL停用或减量,所有患者均无明显不良反应。结论:对重症/难治性心脏大血管受累的BS患者,应用GOL与糖皮质激素和免疫抑制剂/调节剂联合治疗,有助于安全、有效控制病情,降低炎症反应,减少术后严重并发症和糖皮质激素用量。Objective:To explore the effectiveness and safety of golimumab in the treatment of severe/refractory cardiovascular Behcet syndrome(BS).Methods:We retrospectively analyzed the clinical data of nine patients diagnosed with severe/refractory cardiovascular BS and treated with golimumab from February 2018 to July 2020 in Peking Union Medical College Hospital.We analyzed levels of erythrocyte sedimentation rate(ESR)and high-sensitivity C-reactive protein(hsCRP),imaging findings,and the doses of glucocorticoids and immunosuppressive agents during the period of combined treatment with golimumab.Results:Nine patients were enrolled,including 8 males and 1 female,with a mean age and median course of(37.0±8.6)years and 120(60,132)months,respectively.Seven patients presented with severe aortic regurgitation combined with other cardiovascular involvement secondary to BS.Two patients presented with large vessel involvement,including multiple aneurysms and vein thrombosis.Prior to golimumab treatment,seven patients were treated with glucocorticoids and multiple immunosuppres-sants[with a median number of 3(1,3)types]while still experienced disease progression or elevated inflammation biomarkers during postoperative period.Eight patients with disease progression,uncontrolled inflammation and history of severe postoperative complications required effective and fast control of inflammation during perioperative period.One patient had adverse reaction with tocilizumab and switched to golimumab during perioperative period.The patients were treated with golimumab 50 mg every 4 weeks,along with concomitant treatment of glucocorticoid and immunosuppressants.After a median follow-up of(16.3±5.6)months,all the patients achieved clinical improvement.Vascular lesions were radiologically stable and no vascular progressive or newly-onset of vascular lesions was observed.The eight patients who experienced cardiac or vascular operations showed no evidence of postoperative complications.The ESR and hsCRP levels decreased significantly[16.5(6.

关 键 词：白塞综合征 戈利木单抗 心脏瓣膜疾病 大血管受累 

分 类 号：R597.9[医药卫生—内科学]