Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2020, Vol. 52 ›› Issue (6): 1056-1062. doi: 10.19723/j.issn.1671-167X.2020.06.011

Previous Articles     Next Articles

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)

RICH HTML

 5   

PDF (PC)

167

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

CLC Number: 

  • R597.9

Table 1

Clinical characteristics of BS patients with cardiac/large vessel involvement"

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

Figure 1

Changes of ESR during GOL treatment Number 1-9, the patient number; GOL, golimumab; ESR, erythrocyte sedimentation rate."

Figure 2

Changes of hsCRP during GOL treatment Number 1-9, the patient number; GOL, golimumab; hsCRP, high-sensitivity C-reactive protein."

[1] Takeuchi M, Kastner DL, Remmers EF. The immunogenetics of Behcet’s disease: A comprehensive review[J]. J Autoimmun, 2015,64:137-148.
pmid: 26347074
[2] Zeidan MJ, Saadoun D, Garrido M, et al. Behcet’s disease physiopathology: A contemporary review[J]. Auto Immun Highlights, 2016,7(1):4.
doi: 10.1007/s13317-016-0074-1 pmid: 26868128
[3] Sakane T, Takeno M, Suzuki N, et al. Behcet’s disease[J]. N Engl J Med, 1999,341(17):1284-1291.
doi: 10.1056/NEJM199910213411707 pmid: 10528040
[4] Geri G, Wechsler B, Thi Huong du L, et al. Spectrum of cardiac lesions in Behcet’s disease: A series of 52 patients and review of the literature[J]. Medicine (Baltimore), 2012,91(1):25-34.
doi: 10.1097/MD.0b013e3182428f49
[5] 郑文洁. 重视白塞病血管病变[J]. 中华风湿病学杂志, 2016,20(12):793-795.
[6] Merashli M, Eid RE, Uthman I. A review of current management of vasculo-Behcet’s[J]. Curr Opin Rheumatol, 2018,30(1):50-56.
doi: 10.1097/BOR.0000000000000458 pmid: 29076891
[7] Vitale A, Emmi G, Lopalco G, et al. Long-term efficacy and safety of golimumab in the treatment of multirefractory Behcet’s disease[J]. Clin Rheumatol, 2017,36(9):2063-2069.
pmid: 28401434
[8] Fabiani C, Sota J, Rigante D, et al. Rapid and sustained efficacy of golimumab in the treatment of multirefractory uveitis associated with Behcet’s disease[J]. Ocul Immunol Inflamm, 2019,27(1):58-63.
doi: 10.1080/09273948.2017.1351573 pmid: 28981395
[9] International Team for the Revision of the International Criteria for Behcet’s Disease (ITR-ICBD). The International Criteria for Behcet’s Disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria[J]. J Eur Acad Dermatol Venereol, 2014,28(3):338-347.
pmid: 23441863
[10] Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group[J]. Am J Clin Oncol, 1982,5(6):649-655.
pmid: 7165009
[11] Duzgun N, Ates A, Aydintug OT, et al. Characteristics of vascular involvement in Behcet’s disease[J]. Scand J Rheumatol, 2006,35(1):65-68.
pmid: 16467046
[12] Seyahi E, Yazici H. Behcet’s syndrome: Pulmonary vascular disease[J]. Curr Opin Rheumatol, 2015,27(1):18-23.
doi: 10.1097/BOR.0000000000000131 pmid: 25415527
[13] Alibaz-Oner F, Karadeniz A, Ylmaz S, et al. Behcet disease with vascular involvement: effects of different therapeutic regimens on the incidence of new relapses[J]. Medicine (Baltimore), 2015,94(6):e494.
[14] Hamuryudan V, Er T, Seyahi E, et al. Pulmonary artery aneurysms in Behcet syndrome[J]. Am J Med, 2004,117(11):867-870.
doi: 10.1016/j.amjmed.2004.05.027 pmid: 15589493
[15] Saadoun D, Asli B, Wechsler B, et al. Long-term outcome of arterial lesions in Behcet disease: a series of 101 patients[J]. Medicine (Baltimore), 2012,91(1):18-24.
[16] Seyahi E, Melikoglu M, Akman C, et al. Pulmonary artery involvement and associated lung disease in Behcet disease: a series of 47 patients[J]. Medicine (Baltimore), 2012,91(1):35-48.
[17] Emmi G, Silvestri E, Squatrito D, et al. Thrombosis in vasculitis: from pathogenesis to treatment[J]. Thromb J, 2015,13:15.
doi: 10.1186/s12959-015-0047-z pmid: 25883536
[18] Onur E, Kabaroglu C, Inanir I, et al. Oxidative stress impairs endothelial nitric oxide levels in Behcet’s disease[J]. Cutan Ocul Toxicol, 2011,30(3):217-220.
doi: 10.3109/15569527.2011.554480 pmid: 21345164
[19] Pfeiler S, Stark K, Massberg S, et al. Propagation of thrombosis by neutrophils and extracellular nucleosome networks[J]. Haematologica, 2017,102(2):206-213.
doi: 10.3324/haematol.2016.142471 pmid: 27927771
[20] Zhou ZY, Chen SL, Shen N, et al. Cytokines and Behcet’s disease[J]. Autoimmun Rev, 2012,11(10):699-704.
pmid: 22197901
[21] Tong B, Liu X, Xiao J, et al. Immunopathogenesis of Behcet’s disease[J]. Front Immunol, 2019,10:665.
doi: 10.3389/fimmu.2019.00665 pmid: 30984205
[22] van der Houwen T, van Laar J. Behet’s disease, and the role of TNF-alpha and TNF-alpha blockers[J]. Int J Mol Sci, 2020,21(9):3072.
[23] Lee EB, Kim JY, Lee YJ, et al. TNF and TNF receptor polymorphisms in Korean Behcet’s disease patients[J]. Hum Immunol, 2003,64(6):614-620.
doi: 10.1016/s0198-8859(03)00057-0 pmid: 12770792
[24] Dalghous AM, Freysdottir J, Fortune F. Expression of cytokines, chemokines, and chemokine receptors in oral ulcers of patients with Behcet’s disease (BD) and recurrent aphthous stomatitis is Th1-associated, although Th2-association is also observed in patients with BD[J]. Scand J Rheumatol, 2006,35(6):472-475.
doi: 10.1080/03009740600905380 pmid: 17343257
[25] El-Asrar AM, Struyf S, Kangave D, et al. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis[J]. Clin Immunol, 2011,139(2):177-184.
doi: 10.1016/j.clim.2011.01.014 pmid: 21334264
[26] Emmi G, Silvestri E, Bella CD, et al. Cytotoxic Th1 and Th17 cells infiltrate the intestinal mucosa of Behcet patients and exhibit high levels of TNF-alpha in early phases of the disease[J]. Medicine (Baltimore), 2016,95(49):e5516.
doi: 10.1097/MD.0000000000005516
[27] Aksoy A, Yazici A, Omma A, et al. Efficacy of TNFalpha inhibitors for refractory vascular Behcet’s disease: A multicenter observational study of 27 patients and a review of the literature[J]. Int J Rheum Dis, 2020,23(2):256-261.
doi: 10.1111/1756-185X.13778 pmid: 31976619
[28] Chan E, Sangle SR, Coghlan JG, et al. Pulmonary artery aneurysms in Behcet’s disease treated with anti-TNFalpha: A case series and review of the literature[J]. Autoimmun Rev, 2016,15(4):375-378.
doi: 10.1016/j.autrev.2016.01.003 pmid: 26777307
[29] Hamuryudan V, Seyahi E, Ugurlu S, et al. Pulmonary artery involvement in Behcet’s syndrome: Effects of anti-TNF treatment[J]. Semin Arthritis Rheum, 2015,45(3):369-373.
doi: 10.1016/j.semarthrit.2015.06.008 pmid: 26190564
[30] Desbois AC, Biard L, Addimanda O, et al. Efficacy of anti-TNF alpha in severe and refractory major vessel involvement of Behcet’s disease: A multicenter observational study of 18 patients[J]. Clin Immunol, 2018,197:54-59.
doi: 10.1016/j.clim.2018.08.004 pmid: 30125675
[31] Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behcet’s syndrome[J]. Ann Rheum Dis, 2018,77(6):808-818.
doi: 10.1136/annrheumdis-2018-213225 pmid: 29625968
[32] 李璐, 刘金晶, 郁欣, 等. 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[J]. 中华内科杂志, 2020,59(4):303-308.
[33] Thomas SS, Borazan N, Barroso N, et al. Comparative immunogenicity of TNF inhibitors: impact on clinical efficacy and tolerability in the management of autoimmune diseases. A systematic review and meta-analysis[J]. Bio Drugs, 2015,29(4):241-258.
[34] Svedbom A, Storck C, Kachroo S, et al. Persistence with golimumab in immune-mediated rheumatic diseases: a systematic review of real-world evidence in rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis[J]. Patient Prefer Adherence, 2017,11:719-729.
doi: 10.2147/PPA.S128665 pmid: 28435230
[35] Kawalec P, Pilc A. An indirect comparison of infliximab versus adalimumab or golimumab for active ulcerative colitis[J]. Arch Med Sci, 2016,12(5):1097-1109.
pmid: 27695502
[36] Shealy D, Cai A, Staquet K, et al. Characterization of golimu-mab, a human monoclonal antibody specific for human tumor necrosis factor α[J]. MAbs, 2010,2(4):428-439.
pmid: 20519961
[37] Sánchez-Cano D, Callejas-Rubio JL, Ruiz-Villaverde R, et al. Off-label uses of anti-TNF therapy in three frequent disorders: Behcet’s disease, sarcoidosis, and noninfectious uveitis[J]. Mediators Inflamm, 2013,2013:286857. doi: 10.1155/2013/286857.
doi: 10.1155/2013/286857 pmid: 23983404
[38] Zhou H, Jang H, Fleischmann RM, et al. Pharmacokinetics and safety of golimumab, a fully human anti-TNF-alpha monoclonal antibody, in subjects with rheumatoid arthritis[J]. J Clin Pharmacol, 2007,47(3):383-396.
doi: 10.1177/0091270006298188 pmid: 17322150
[39] Keystone EC, Genovese MC, Klareskog L, et al. Golimumab, a human antibody to tumour necrosis factor alpha given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study[J]. Ann Rheum Dis, 2009,68(6):789-796.
doi: 10.1136/ard.2008.099010 pmid: 19066176
[40] Smolen JS, Kay J, Doyle MK, et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, rando-mised, double-blind, placebo-controlled, phase III trial[J]. Lancet, 2009,374(9685):210-221.
doi: 10.1016/S0140-6736(09)60506-7
[41] Boyce EG, Halilovic J, Stan-Ugbene O. Golimumab: Review of the efficacy and tolerability of a recently approved tumor necrosis factor-alpha inhibitor[J]. Clin Ther, 2010,32(10):1681-1703.
doi: 10.1016/j.clinthera.2010.09.003
[42] Pelechas E, Voulgari PV, Drosos AA. Golimumab for rheumatoid arthritis[J]. J Clin Med, 2019,8(3):387.
doi: 10.3390/jcm8030387
[43] Papagoras C, Voulgari PV, Drosos AA. Golimumab, the newest TNF-alpha blocker, comes of age[J]. Clin Exp Rheumatol, 2015,33(4):570-577.
pmid: 25602858
[44] Pappas DA, St John G, Etzel CJ, et al. Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study [J]. Ann Rheum Dis, 2020, annrheumdis-2020-217209. doi: 10.1136/annrheumdis-2020-217209.
doi: 10.1136/annrheumdis-2020-218186 pmid: 33243781
[45] Yokota S, Imagawa T, Mori M, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase Ⅲ trial[J]. Lancet, 2008,371(9617):998-1006.
doi: 10.1016/S0140-6736(08)60454-7 pmid: 18358927
[46] Strangfeld A, Richter A, Siegmund B, et al. Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs[J]. Ann Rheum Dis, 2017,76(3):504-510.
doi: 10.1136/annrheumdis-2016-209773 pmid: 27405509
[1] Dong YAN,Wen-jie ZHENG. Progress in interferon: A treatment of Behcet syndrome [J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1166-1170.
[2] Chen YU,Chun LI,Yang-yi FAN,Yan XU. Co-existence of Guillain-Barré syndrome and Behcet syndrome: A case report [J]. Journal of Peking University (Health Sciences), 2020, 52(6): 1146-1149.
[3] WANG Yu, YANG Liu, ZHANG Zhuo-li. Panuveitis with oral and genital ulcer misdiagnosed as Behcet’s disease: two cases report and literature review [J]. Journal of Peking University(Health Sciences), 2016, 48(5): 910-913.
[4] HUANG Qing, WANG Xue-mei, LIU Yu-lan, FENG Gui-jian, YOU Peng.  Capsule endoscopy for Behcet’s disease-treatment: five cases reports [J]. Journal of Peking University(Health Sciences), 2016, 48(2): 366-369.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Journal of Peking University(Health Sciences), 2009, 41(3): 376 -379 .
[2] . [J]. Journal of Peking University(Health Sciences), 2009, 41(4): 459 -462 .
[3] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 319 -322 .
[4] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 333 -336 .
[5] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 337 -340 .
[6] . [J]. Journal of Peking University(Health Sciences), 2007, 39(3): 225 -328 .
[7] . [J]. Journal of Peking University(Health Sciences), 2007, 39(4): 351 -354 .
[8] . [J]. Journal of Peking University(Health Sciences), 2007, 39(4): 361 -364 .
[9] . [J]. Journal of Peking University(Health Sciences), 2007, 39(4): 369 -373 .
[10] . [J]. Journal of Peking University(Health Sciences), 2007, 39(4): 377 -380 .
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd