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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (6): 1056-1062. doi: 10.19723/j.issn.1671-167X.2020.06.011

• 论著 • 上一篇    下一篇

戈利木单抗治疗白塞综合征心脏大血管受累的临床分析

孙鹿希1,刘金晶1,侯云霞2,李超然1,李璐1,田新平1,曾小峰1,郑文洁1,△()   

  1. 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
  • 收稿日期:2020-07-30 出版日期:2020-12-18 发布日期:2020-12-13
  • 通讯作者: 郑文洁 E-mail:zhengwj@pumch.cn
  • 基金资助:
    国家自然科学基金(81871299)

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

Lu-xi SUN1,Jin-jing LIU1,Yun-xia HOU2,Chao-ran LI1,Lu LI1,Xin-ping TIAN1,Xiao-feng ZENG1,Wen-jie ZHENG1,△()   

  1. 1. 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
    2. Department of Rheumatology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
  • Received:2020-07-30 Online:2020-12-18 Published:2020-12-13
  • Contact: Wen-jie ZHENG E-mail:zhengwj@pumch.cn
  • Supported by:
    National Natural Science Foundation of China(81871299)

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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。

关键词: 白塞综合征, 戈利木单抗, 心脏瓣膜疾病, 大血管受累

Abstract:

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 (6.8, 52.5) mm/h vs. 4 (2, 7) mm/h, and 21.24 (0.93, 32.51) mg/L vs. 0.58 (0.37, 1.79) mg/L (P<0.05), respectively]. The dose of prednisone was tapered from 35 (15, 60) mg/d to 10.0 (10.0, 12.5) mg/d. No prominent adverse reactions were observed. Conclusion: Our study suggests that golimumab is effective in the treatment of severe/refractory cardiovascular BS. Combination immunosuppression therapy with golimumab contributes to control of inflammation, reduction of postoperative complications and tapering the dose of glucocorticoids or immunosuppressants.

Key words: Behcet syndrome, Golimumab, Heart valve diseases, Large vessel involvement

中图分类号: 

  • R597.9

表1

心脏/大血管受累BS患者的临床特征"

No. Age/
Gender		 Disease
course/
years		 Systemic
involvement		 Vascular/cardiac
manifestations, previous
surgeries and
postoperative complications		 Previous
treatment		 Concomitant
therapy		 Operations (with
perioperative GOL)		 Duration
of GOL
treatment/
months		 Follow-up/
months		 Outcome
1 29/M 5 O,G,S Abdominal aortic pseudoa-neurysm, superior mesenteric aneurysm, occlusion, stenosis of the abdominal trunk GCS, CTX, THD GCS, CTX, LEF, THD Endovascular repair of aneurysm 5 18 No progression of
vascular
lesions
2 37/M 25 O,G,S,P Pulmonary aneurysm, pulmonary thrombosis, deep vein thrombosis of lower extremities - GCS, CTX Pulmonary aneurysm packing + bronchial aneurysm embolization 8 8 Reduced size of
aneurysms, no progression of vascular
lesions
3 35/M 11 O,G,S,A AR, valvular vegetation-like mobile lesions, paravalvular abscess, stenosis of lower limb arteries GCS, CTX, COL, THD, TCZ GCS, CTX, AZA, COL Bentall procedure + MVR 23 23 No PVL
4 38/M 10 O,G,S AR, paravalvular abscess GCS, CTX GCS, CTX Bentall procedure 17 17 No PVL
5 30/M 1 O,S AR, aortic dissection, aortic dilation, aneurysm of aortic sinus GCS, CTX, AZA, COL, T II GCS, CTX, AZA, T II Bentall procedure 12 16 No PVL
6 34/M 20 O AR, aortic dilation GCS, CTX, THD CTX, THD None 22 22 Relieved aortic
regurgitation,
avoided surgical
intervention
7 57/F 6 O,G,S,A AR, MR - GCS, CTX AVR 10 13 No PVL
8 31/M 3 O,S AR, MR, TR, valvular ve-getation-like mobile lesions, aortic dilation, aneurysm of aortic sinus, post-cardiac operation, PVL GCS, CTX, MTX, MMF, COL GCS, CTX, MTX, MMF, COL Bentall procedure 8 8 No PVL
9 30/M 10 O,S AR, MR, TR, paravalvular abscess, aortic dilation, post-cardiac operation, PVL twice GCS, CTX, AZA, COL, THD GCS, AZA, COL, THD Bentall procedure + MVR + TVP 6 21 No PVL

图1

GOL治疗后ESR的变化"

图2

GOL治疗后hsCRP的变化"

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