Biological Agent Use in Behçet's Patients Who Are Resistant to Conventional Treatments: A Multidisciplinary Retrospective Study

Abstract

Background Comparing treatment modalities is difficult in Behcet's syndrome, even if tumour necrosis factor-alpha (TNF-α) inhibitors are a treatment option for all involvements resistant to conventional therapy. This study evaluated how different departments dealt with treatment, particularly with TNF-α inhibitors. Material and Methods The study comprised 111 patients from our Behcet's syndrome cohort who were treated with TNF-α inhibitors between 2010 and 2019. Data on patients were retrieved retrospectively from the rheumatology, ophthalmology, and dermatology clinics' patient records. Results Patients followed up in rheumatology (n: 40) were classified as Group 1, and patients followed up in ophthalmology (n: 49) and dermatology (n: 5) as Group 2. In Group 1, genital ulcers, erythema nodosum (p=0.009, p=0.003, respectively), lower extremity deep vein thrombosis, arterial aneurysm and neurological involvement were more common (p=0.005, p=0.008, p=0.001, respectively). In Group 2, the use of cyclosporine and interferon-α before the anti-TNF agent was higher (p<0.001, p<0.001, respectively), and the use of cyclophosphamide were higher in Group 1 (p<0.001). Both groups preferred infliximab, and ocular involvement was the most common reason for starting. Conclusions While TNF-α inhibitors were chosen equally across departments, conventional medicines, including cyclosporine, cyclophosphamide, and interferon-α, were not. This choice was determined by the departments' experience and the clinical traits that predominated.

Keywords

• Behcet
• dermatology
• ophthalmology
• rheumatology
• TNF-α inhibitor

References

1. Yazici H, Seyahi E, Hatemi G, Yazici Y. Behçet syndrome: A contemporary view. Nat Rev Rheumatol. 2018; 14:119. doi:10.1038/nrrheum.2018.3.
2. Kural-Seyahi E, Fresko I, Seyahi N, Ozyazgan Y, Mat C, Hamuryudan V, Yurdakul S, Yazici H. The long-term mortality and morbidity of Behçet syndrome: A 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore). 2003 Jan;82(1):60-76. doi: 10.1097/00005792-200301000-00006.
3. Seyahi E. Phenotypes in Behçet’s syndrome. Intern Emerg Med. 2019 Aug;14(5):677-689. doi: 10.1007/s11739-019-02046-y.
4. Azizlerli G, Köse AA, Sarica R, Gül A, Tutkun IT, Kulaç M, Tunç R, Urgancioğlu M, Dişçi R. Prevalence of Behçet’s disease in Istanbul, Turkey. Int J Dermatol. 2003 Oct;42(10):803-6. doi: 10.1046/j.1365-4362.2003.01893.x.
5. Esatoğlu SN, Özgüler Y. Behcet's disease: Current treatment. In: Seyahi E, ed. Türkiye Klinikleri Rheumatology. Behcet's disease. 1st ed. Ankara: 2020:98-104.
6. Seyahi E, Fresko I, Melikoglu M, Yazici H. The management of Behçet’s syndrome. Acta Reumatol Port. 2006 Apr-Jun;31(2):125-31.
7. Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kötter I, Leccese P, Mahr A, Moots R, Ozguler Y, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H. 2018 Update of the EULAR recommendations for the management of Behçet’s syndrome. Ann Rheum Dis. 2018 Jun;77(6):808-818. doi: 10.1136/annrheumdis-2018-213225.
8. Esatoglu SN, Hatemi G. Update on the treatment of Behçet’s syndrome. Intern Emerg Med. 2019 Aug;14(5):661-675. doi: 10.1007/s11739-019-02035-1.

9. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huseyin Altunbas H, Urgancioglu M. Uveitis in Behçet disease: An analysis of 880 patients. Am J Ophthalmol. 2004 Sep;138(3):373-80. doi: 10.1016/j.ajo.2004.03.022.
10. Ozyazgan Y, Ucar D, Hatemi G, Yazici Y. Ocular Involvement of Behçet’s Syndrome: A Comprehensive Review. Clin Rev Allergy Immunol. 2015 Dec;49(3):298-306. doi: 10.1007/s12016-014-8425-z.
11. Üsküdar Cansu D. Behcet's disease: Prognosis. In: Seyahi E, ed. Türkiye Klinikleri Rheumatology. Behcet's disease. 1st ed. Ankara: 2020:93-97.
12. Uçar D, Özyazgan Y. Behcet's disease: Ocular iInvolvement. In: Seyahi E, ed. Türkiye Klinikleri Rheumatology. Behcet's disease. 1st ed. Ankara: 2020:35-42.
13. Tunc R, Keyman E, Melikoglu M, Fresko I, Yazici H. Target organ associations in Turkish patients with Behçet’s disease: A cross sectional study by exploratory factor analysis. J Rheumatol. 2002 Nov;29(11):2393-6.
14. Zouboulis CC, Turnbull JR, Martus P. Univariate and multivariate analyses comparing demographic, genetic, clinical, and serological risk factors for severe Adamantiades-Behçet’s disease. Adv Exp Med Biol. 2003;528:123-6. doi: 10.1007/0-306-48382-3_24.
15. Tanaka C, Matsuda T, Hayashi E, Imamura Y, Ozaki S. Clinical manifestations and course of 200 Japanese patients with Behçet's disease. Adv Exp Med Biol. 2003;528:77-9. doi: 10.1007/0-306-48382-3_14.
16. Bang D, Yoon KH, Chung HG, Choi EH, Lee ES, Lee S. Epidemiological and Clinical Features of Behçet’s Disease in Korea. Yonsei Med J. 1997 Dec;38(6):428-36. doi: 10.3349/ymj.1997.38.6.428.
17. Korkmaz C. Behcet's disease: Epidemiology. In: Seyahi E, ed. Türkiye Klinikleri Rheumatology. Behcet's disease. 1st ed. Ankara: 2020:13-6.
18. Ozguler Y, Leccese P, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Çelik AF, Fortune F, Gaudric J, Gul A, Kötter I, Mahr A, Moots RJ, Richter J, Saadoun D, Salvarani C, Scuderi F, Sfikakis PP, Siva A, Stanford M, Tugal-Tutkun I, West R, Yurdakul S, Olivieri I, Yazici H, Hatemi G. Management of major organ involvement of Behçet's syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford). 2018 Dec 1;57(12):2200-12. doi: 10.1093/rheumatology/key242.
19. Capella MJ, Foster CS. Long-term efficacy and safety of infliximab in the treatment of behçet’s disease. Ocul Immunol Inflamm. 2012 Jun;20(3):198-202. doi: 10.3109/09273948.2012.670360.
20. Niccoli L, Nannini C, Benucci M, Chindamo D, Cassarà E, Salvarani C, Cimino L, Gini G, Lenzetti I, Cantini F. Long-term efficacy of infliximab in refractory posterior uveitis of Behçet’s disease: A 24-month follow-up study. Rheumatology (Oxford). 2007 Jul;46(7):1161-4. doi: 10.1093/rheumatology/kem101.
21. Accorinti M, Pirraglia MP, Paroli MP, Priori R, Conti F, Pivetti-Pezzi P. Infliximab treatment for ocular and extraocular manifestations of Behçet’s disease. Jpn J Ophthalmol. 2007 May-Jun;51(3):191-6. doi: 10.1007/s10384-006-0425-y.
22. Interlandi E, Leccese P, Olivieri I, Latanza L. Adalimumab for treatment of severe Behçet’s uveitis: a retrospective long-term follow-up study. Clin Exp Rheumatol. 2014 Jul-Aug;32(4 Suppl 84):S58-62.