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Update on the treatment of Behçet’s syndrome

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Abstract

Behçet’s syndrome (BS) is a complex disease that shows important heterogeneity in clinical findings and physiopathology. Its treatment can be problematic as BS manifestations in different organs may respond differently to the same drug. The cornerstone of therapy for inducing remission is corticosteroids whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent further relapses. However, a considerable number of patients continue to have mucocutaneous lesions despite therapy, and some patients require more aggressive treatment for refractory major organ involvement. Tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, are increasingly used for various refractory BS manifestations despite the lack of controlled studies. In this review, we aim to focus on both the traditional and new treatment modalities for BS, with more emphasis on recent data on newer agents.

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References

  1. Hatemi G, Christensen R, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter 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) 2018 update of the EULAR recommendations for the management of Behcet’s syndrome. Ann Rheum Dis 77(6):808–818. https://doi.org/10.1136/annrheumdis-2018-213225

    Article  PubMed  Google Scholar 

  2. Aktulga E, Altac M, Muftuoglu A, Ozyazgan Y, Pazarli H, Tuzun Y, Yalcin B, Yazici H, Yurdakul S (1980) A double blind study of colchicine in Behcet’s disease. Haematologica 65(3):399–402

    CAS  PubMed  Google Scholar 

  3. Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Hamuryudan V, Uysal O, Senocak M, Yazici H (2001) A double-blind trial of colchicine in Behcet’s syndrome. Arthritis Rheum 44(11):2686–2692

    Article  CAS  PubMed  Google Scholar 

  4. Davatchi F, Sadeghi Abdollahi B, Tehrani Banihashemi A, Shahram F, Nadji A, Shams H, Chams-Davatchi C (2009) Colchicine versus placebo in Behcet’s disease: randomized, double-blind, controlled crossover trial. Mod Rheumatol 19(5):542–549. https://doi.org/10.1007/s10165-009-0200-2

    Article  CAS  PubMed  Google Scholar 

  5. Leccese P, Ozguler Y, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter 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 (2018) Management of skin, mucosa and joint involvement of Behcet’s syndrome: A systematic review for update of the EULAR recommendations for the management of Behcet’s syndrome. Semin Arthritis Rheum. https://doi.org/10.1016/j.semarthrit.2018.05.008

  6. Yazici H, Pazarli H, Barnes CG, Tuzun Y, Ozyazgan Y, Silman A, Serdaroglu S, Oguz V, Yurdakul S, Lovatt GE et al (1990) A controlled trial of azathioprine in Behcet’s syndrome. N Engl J Med 322(5):281–285. https://doi.org/10.1056/NEJM199002013220501

    Article  CAS  PubMed  Google Scholar 

  7. Hamuryudan V, Mat C, Saip S, Ozyazgan Y, Siva A, Yurdakul S, Zwingenberger K, Yazici H (1998) Thalidomide in the treatment of the mucocutaneous lesions of the Behcet syndrome A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128(6):443–450

    Article  CAS  PubMed  Google Scholar 

  8. Alpsoy E, Durusoy C, Yilmaz E, Ozgurel Y, Ermis O, Yazar S, Basaran E (2002) Interferon alfa-2a in the treatment of Behcet disease: a randomized placebo-controlled and double-blind study. Arch Dermatol 138(4):467–471

    Article  CAS  PubMed  Google Scholar 

  9. Azizlerli G, Sarica R, Kose A, Ovul C, Kavala M, Kayabali M, Erkan F, Kural Z (1996) Interferon alfa-2a in the treatment of Behcet’s disease. Dermatology 192(3):239–241. https://doi.org/10.1159/000246374

    Article  CAS  PubMed  Google Scholar 

  10. Hamuryudan V, Moral F, Yurdakul S, Mat C, Tuzun Y, Ozyazgan Y, Direskeneli H, Akoglu T, Yazici H (1994) Systemic interferon alpha 2b treatment in Behcet’s syndrome. J Rheumatol 21(6):1098–1100

    CAS  PubMed  Google Scholar 

  11. Boyvat A, Sisman-Solak C, Gurler A (2000) Long-term effects of interferon alpha 2A treatment in Behcet’s disease. Dermatology 201(1):40–43. https://doi.org/10.1159/000018427

    Article  CAS  PubMed  Google Scholar 

  12. Alpsoy E, Yilmaz E, Basaran E (1994) Interferon therapy for Behcet’s disease. J Am Acad Dermatol 31(4):617–619

    Article  CAS  PubMed  Google Scholar 

  13. O’Duffy JD, Calamia K, Cohen S, Goronzy JJ, Herman D, Jorizzo J, Weyand C, Matteson E (1998) Interferon-alpha treatment of Behcet’s disease. J Rheumatol 25(10):1938–1944

    PubMed  Google Scholar 

  14. Georgiou S, Monastirli A, Pasmatzi E, Gartaganis S, Goerz G, Tsambaos D (1998) Efficacy and safety of systemic recombinant interferon-alpha in Behcet’s disease. J Intern Med 243(5):367–372

    Article  CAS  PubMed  Google Scholar 

  15. Keskin Y, Seyahi E, Poyraz C, Ugurlu S, Ozyazgan Y, Yazici H (2014) Interferon alfa-associated depression in patients with Behcet’s syndrome: a prospective controlled study. Clin Exp Rheumatol 32(4 Suppl 84):S175

    PubMed  Google Scholar 

  16. Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul S, Hamuryudan V, Yazici H (2005) Short-term trial of etanercept in Behcet’s disease: a double blind, placebo controlled study. J Rheumatol 32(1):98–105

    CAS  PubMed  Google Scholar 

  17. Arida A, Fragiadaki K, Giavri E, Sfikakis PP (2011) Anti-TNF agents for Behcet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum 41(1):61–70. https://doi.org/10.1016/j.semarthrit.2010.09.002

    Article  CAS  PubMed  Google Scholar 

  18. Hatemi G, Melikoglu M, Tunc R, Korkmaz C, Turgut Ozturk B, Mat C, Merkel PA, Calamia KT, Liu Z, Pineda L, Stevens RM, Yazici H, Yazici Y (2015) Apremilast for Behcet’s syndrome–a phase 2, placebo-controlled study. N Engl J Med 372(16):1510–1518. https://doi.org/10.1056/NEJMoa1408684

    Article  CAS  PubMed  Google Scholar 

  19. Hatemi G, Mahr A, Takeno M, Kim DY, Melikoglu M, Cheng S, McCue S, Paris M, Wang Y, Yazici Y (2018) Apremilast for Behçet’s syndrome: a phase iii randomised, placebo-controlled, double-blind study (RELIEF). Ann Rheum Dis 77:91–92

    Article  Google Scholar 

  20. Vitale A, Rigante D, Lopalco G, Emmi G, Bianco MT, Galeazzi M, Iannone F, Cantarini L (2016) New therapeutic solutions for Behcet’s syndrome. Expert Opin Investig Drugs 25(7):827–840. https://doi.org/10.1080/13543784.2016.1181751

    Article  CAS  PubMed  Google Scholar 

  21. Vitale A, Rigante D, Lopalco G, Selmi C, Galeazzi M, Iannone F, Cantarini L (2016) Interleukin-1 Inhibition in Behcet’s disease. Isr Med Assoc J 18(3–4):171–176

    PubMed  Google Scholar 

  22. Cantarini L, Vitale A, Scalini P, Dinarello CA, Rigante D, Franceschini R, Simonini G, Borsari G, Caso F, Lucherini OM, Frediani B, Bertoldi I, Punzi L, Galeazzi M, Cimaz R (2015) Anakinra treatment in drug-resistant Behcet’s disease: a case series. Clin Rheumatol 34(7):1293–1301. https://doi.org/10.1007/s10067-013-2443-8

    Article  PubMed  Google Scholar 

  23. Emmi G, Talarico R, Lopalco G, Cimaz R, Cantini F, Viapiana O, Olivieri I, Goldoni M, Vitale A, Silvestri E, Prisco D, Lapadula G, Galeazzi M, Iannone F, Cantarini L (2016) Efficacy and safety profile of anti-interleukin-1 treatment in Behcet’s disease: a multicenter retrospective study. Clin Rheumatol 35(5):1281–1286. https://doi.org/10.1007/s10067-015-3004-0

    Article  PubMed  Google Scholar 

  24. Grayson PC, Yazici Y, Merideth M, Sen HN, Davis M, Novakovich E, Joyal E, Goldbach-Mansky R, Sibley CH (2017) Treatment of mucocutaneous manifestations in Behcet’s disease with anakinra: a pilot open-label study. Arthritis Res Ther 19(1):69. https://doi.org/10.1186/s13075-017-1222-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mirouse A, Barete S, Monfort JB, Resche-Rigon M, Bouyer AS, Comarmond C, Sene D, Domont F, Ferfar Y, Cacoub P, Saadoun D (2017) Ustekinumab for Behcet’s disease. J Autoimmun 82:41–46. https://doi.org/10.1016/j.jaut.2017.05.002

    Article  CAS  PubMed  Google Scholar 

  26. Shapiro LS, Farrell J, Borhani Haghighi A (2012) Tocilizumab treatment for neuro-Behcet’s disease, the first report. Clin Neurol Neurosurg 114(3):297–298. https://doi.org/10.1016/j.clineuro.2011.10.024

    Article  PubMed  Google Scholar 

  27. Atienza-Mateo B, Calvo-Rio V, Beltran E, Martinez-Costa L, Valls-Pascual E, Hernandez-Garfella M, Atanes A, Cordero-Coma M, Miquel Nolla J, Carrasco-Cubero C, Loricera J, Gonzalez-Vela MC, Vegas-Revenga N, Fernandez-Diaz C, Demetrio-Pablo R, Dominguez-Casas LC, Luis Martin-Varillas J, Palmou-Fontana N, Hernandez JL, Gonzalez-Gay MA, Blanco R (2018) Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcet’s disease: multicentre retrospective study. Rheumatology (Oxford) 57(5):856–864. https://doi.org/10.1093/rheumatology/kex480

    Article  CAS  Google Scholar 

  28. Diamantopoulos AP, Hatemi G (2013) Lack of efficacy of tocilizumab in mucocutaneous Behcet’s syndrome: report of two cases. Rheumatology (Oxford) 52(10):1923–1924. https://doi.org/10.1093/rheumatology/ket130

    Article  Google Scholar 

  29. Hirano T, Ohguro N, Hohki S, Hagihara K, Shima Y, Narazaki M, Ogata A, Yoshizaki K, Kumanogoh A, Kishimoto T, Tanaka T (2012) A case of Behcet’s disease treated with a humanized anti-interleukin-6 receptor antibody, tocilizumab. Mod Rheumatol 22(2):298–302. https://doi.org/10.1007/s10165-011-0497-5

    Article  PubMed  Google Scholar 

  30. Emmi G, Silvestri E, Squatrito D, Emmi L, Cantarini L, Prisco D (2016) Tocilizumab-induced exacerbation of mucosal ulcers in a patient with multi-refractory Behcets disease. Semin Arthritis Rheum 46(1):e1–2. https://doi.org/10.1016/j.semarthrit.2016.03.006

    Article  PubMed  Google Scholar 

  31. Cantarini L, Lopalco G, Vitale A, Coladonato L, Rigante D, Lucherini OM, Lapadula G, Iannone F (2015) Paradoxical mucocutaneous flare in a case of Behcet’s disease treated with tocilizumab. Clin Rheumatol 34(6):1141–1143. https://doi.org/10.1007/s10067-014-2589-z

    Article  PubMed  Google Scholar 

  32. Deroux A, Chiquet C, Bouillet L (2016) Tocilizumab in severe and refractory Behcet’s disease: four cases and literature review. Semin Arthritis Rheum 45(6):733–737. https://doi.org/10.1016/j.semarthrit.2015.11.012

    Article  CAS  PubMed  Google Scholar 

  33. Vitale A, Emmi G, Lopalco G, Fabiani C, Gentileschi S, Silvestri E, Gerardo DS, Iannone F, Frediani B, Galeazzi M, Lapadula G, Rigante D, Cantarini L (2017) Long-term efficacy and safety of golimumab in the treatment of multirefractory Behcet’s disease. Clin Rheumatol 36(9):2063–2069. https://doi.org/10.1007/s10067-017-3627-4

    Article  PubMed  Google Scholar 

  34. Lopalco G, Emmi G, Gentileschi S, Guerriero S, Vitale A, Silvestri E, Becatti M, Cavallo I, Fabiani C, Frediani B, Iannone F, Cantarini L (2017) Certolizumab Pegol treatment in Behcet’s disease with different organ involvement: a multicenter retrospective observational study. Mod Rheumatol 27(6):1031–1035. https://doi.org/10.1080/14397595.2017.1285857

    Article  CAS  PubMed  Google Scholar 

  35. Di Scala G, Bettiol A, Cojan RD, Finocchi M, Silvestri E, Emmi G (2018) Efficacy of the anti-IL 17 secukinumab in refractory Behcet’s syndrome: a preliminary study. J Autoimmun. https://doi.org/10.1016/j.jaut.2018.09.002

  36. Henderson LK, Masson P, Craig JC, Roberts MA, Flanc RS, Strippoli GF, Webster AC (2013) Induction and maintenance treatment of proliferative lupus nephritis: a meta-analysis of randomized controlled trials. Am J Kidney Dis 61(1):74–87. https://doi.org/10.1053/j.ajkd.2012.08.041

    Article  PubMed  Google Scholar 

  37. Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM, Sclerodema Lung Study III (2016) Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med 4(9):708–719. https://doi.org/10.1016/s2213-2600(16)30152-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Smith RM (2015) Update on the treatment of ANCA associated vasculitis. Presse Med 44(6 Pt 2):e241–249. https://doi.org/10.1016/j.lpm.2015.04.008

    Article  PubMed  Google Scholar 

  39. Adler YD, Mansmann U, Zouboulis CC (2001) Mycophenolate mofetil is ineffective in the treatment of mucocutaneous Adamantiades-Behcet’s disease. Dermatology 203(4):322–324. https://doi.org/10.1159/000051781

    Article  CAS  PubMed  Google Scholar 

  40. Kose O, Simsek I, Pay S (2011) Mycophenolate sodium in the treatment of mucocutaneous Behcet’s diseases. Int J Dermatol 50(7):895–896. https://doi.org/10.1111/j.1365-4632.2010.04505.x

    Article  PubMed  Google Scholar 

  41. Calguneri M, Ozturk MA, Ertenli I, Kiraz S, Apras S, Ozbalkan Z (2003) Effects of interferon alpha treatment on the clinical course of refractory Behcet’s disease: an open study. Ann Rheum Dis 62(5):492–493

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kotter I, Vonthein R, Zierhut M, Eckstein AK, Ness T, Gunaydin I, Grimbacher B, Blaschke S, Peter HH, Stubiger N (2004) Differential efficacy of human recombinant interferon-alpha2a on ocular and extraocular manifestations of Behcet disease: results of an open 4-center trial. Semin Arthritis Rheum 33(5):311–319

    Article  PubMed  Google Scholar 

  43. Ozyazgan Y, Ucar D, Hatemi G, Yazici Y (2015) Ocular involvement of Behcet’s syndrome: a comprehensive review. Clin Rev Allergy Immunol 49(3):298–306. https://doi.org/10.1007/s12016-014-8425-z

    Article  PubMed  Google Scholar 

  44. Cunningham ET Jr, Tugal-Tutkun I, Khairallah M, Okada AA, Bodaghi B, Zierhut M (2017) Behcet Uveitis. Ocul Immunol Inflamm 25(1):2–6. https://doi.org/10.1080/09273948.2017.1279840

    Article  PubMed  Google Scholar 

  45. Knickelbein JE, Armbrust KR, Kim M, Sen HN, Nussenblatt RB (2017) Pharmacologic treatment of noninfectious Uveitis. Handb Exp Pharmacol 242:231–268. https://doi.org/10.1007/164_2016_21

    Article  CAS  PubMed  Google Scholar 

  46. Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G (1989) Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behcet’s disease. Lancet 1(8647):1093–1096

    Article  CAS  PubMed  Google Scholar 

  47. Ozyazgan Y, Yurdakul S, Yazici H, Tuzun B, Iscimen A, Tuzun Y, Aktunc T, Pazarli H, Hamuryudan V, Muftuoglu A (1992) Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet’s syndrome: a single masked trial. Br J Ophthalmol 76(4):241–243

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. BenEzra D, Cohen E, Chajek T, Friedman G, Pizanti S, de Courten C, Harris W (1988) Evaluation of conventional therapy versus cyclosporine A in Behcet’s syndrome. Transplant Proc 20(3 Suppl 4):136–143

    CAS  PubMed  Google Scholar 

  49. Kötter I, Vonthein R, Schoenfisch B et al (2016) AB0545 interferon alpha2a versus cyclosporin A for the treatment of severe ocular behcet’s disease – a prospective, randomised, single blind, national multicenter trial (INCYTOB). Ann Rheum Dis 75:1091

    Article  Google Scholar 

  50. Yamada Y, Sugita S, Tanaka H, Kamoi K, Kawaguchi T, Mochizuki M (2010) Comparison of infliximab versus ciclosporin during the initial 6-month treatment period in Behcet disease. Br J Ophthalmol 94(3):284–288. https://doi.org/10.1136/bjo.2009.158840

    Article  PubMed  Google Scholar 

  51. Ozguler Y, Leccese P, Christensen R, Esatoglu SN, Bang D, Bodaghi B, Celik AF, Fortune F, Gaudric J, Gul A, Kotter 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 (2018) Management of major organ involvement of Behcet’s syndrome: a systematic review for update of the EULAR recommendations. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/key242

  52. Markomichelakis N, Delicha E, Masselos S, Fragiadaki K, Kaklamanis P, Sfikakis PP (2011) A single infliximab infusion vs corticosteroids for acute panuveitis attacks in Behcet’s disease: a comparative 4-week study. Rheumatology (Oxford) 50(3):593–597. https://doi.org/10.1093/rheumatology/keq366

    Article  CAS  Google Scholar 

  53. Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB (2016) Adalimumab in patients with active noninfectious Uveitis. N Engl J Med 375(10):932–943. https://doi.org/10.1056/NEJMoa1509852

    Article  CAS  PubMed  Google Scholar 

  54. Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, Schlaen A, Pavesio C, Cimino L, Van Calster J, Camez AA, Kwatra NV, Song AP, Kron M, Tari S, Brezin AP (2016) Adalimumab for prevention of uveitic flare in patients with inactive non-infectious uveitis controlled by corticosteroids (VISUAL II): a multicentre, double-masked, randomised, placebo-controlled phase 3 trial. Lancet 388(10050):1183–1192. https://doi.org/10.1016/S0140-6736(16)31339-3

    Article  CAS  PubMed  Google Scholar 

  55. Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Bitossi A, Orlando I, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2018) Efficacy of adalimumab and infliximab in recalcitrant retinal vasculitis inadequately responsive to other immunomodulatory therapies. Clin Rheumatol. https://doi.org/10.1007/s10067-018-4133-z

  56. Fabiani C, Vitale A, Emmi G, Bitossi A, Lopalco G, Sota J, Guerriero S, Orlando I, Capozzoli M, Fusco F, Rana F, Iannone F, Frediani B, Galeazzi M, Vannozzi L, Tosi GM, Cantarini L (2018) Long-term retention rates of adalimumab and infliximab in non-infectious intermediate, posterior, and panuveitis. Clin Rheumatol. https://doi.org/10.1007/s10067-018-4069-3

  57. Fabiani C, Sota J, Vitale A, Rigante D, Emmi G, Vannozzi L, Bacherini D, Lopalco G, Guerriero S, Gentileschi S, Capozzoli M, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2018) Cumulative retention rate of adalimumab in patients with Behcet’s disease-related uveitis: a four-year follow-up study. Br J Ophthalmol 102(5):637–641. https://doi.org/10.1136/bjophthalmol-2017-310733

    Article  PubMed  Google Scholar 

  58. Martin-Varillas JL, Calvo-Rio V, Beltran E, Sanchez-Burson J, Mesquida M, Adan A, Hernandez MV, Garfella MH, Pascual EV, Martinez-Costa L, Sellas-Fernandez A, Cordero-Coma M, Diaz-Llopis M, Gallego R, Salom D, Ortego N, Garcia-Serrano JL, Callejas-Rubio JL, Herreras JM, Garcia-Aparicio A, Maiz O, Blanco A, Torre I, Diaz-Valle D, Pato E, Aurrecoechea E, Caracuel MA, Gamero F, Minguez E, Carrasco-Cubero C, Olive A, Vazquez J, Ruiz-Moreno O, Manero J, Munoz-Fernandez S, Martinez MG, Rubio-Romero E, Toyos-Saenz de Miera FJ, Lopez Longo FJ, Nolla JM, Revenga M, Gonzalez-Vela C, Loricera J, Atienza-Mateo B, Demetrio-Pablo R, Hernandez JL, Gonzalez-Gay MA, Blanco R (2018) Successful optimization of adalimumab therapy in refractory uveitis due to Behcet’s disease. Ophthalmology 125(9):1444–1451. https://doi.org/10.1016/j.ophtha.2018.02.020

    Article  PubMed  Google Scholar 

  59. Vitale A, Emmi G, Lopalco G, Gentileschi S, Silvestri E, Fabiani C, Urban ML, Frediani B, Galeazzi M, Iannone F, Rigante D, Cantarini L (2017) Adalimumab effectiveness in Behcet’s disease: short and long-term data from a multicenter retrospective observational study. Clin Rheumatol 36(2):451–455. https://doi.org/10.1007/s10067-016-3417-4

    Article  PubMed  Google Scholar 

  60. Dick AD, Tugal-Tutkun I, Foster S, Zierhut M, Melissa Liew SH, Bezlyak V, Androudi S (2013) Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 120(4):777–787. https://doi.org/10.1016/j.ophtha.2012.09.040

    Article  PubMed  Google Scholar 

  61. Tugal-Tutkun I, Pavesio C, De Cordoue A, Bernard-Poenaru O, Gul A (2018) Use of gevokizumab in patients with Behcet’s disease uveitis: an international, randomized, double-masked, placebo-controlled study and open-label extension study. Ocul Immunol Inflamm. https://doi.org/10.1080/09273948.2017.1421233

  62. Lightman S, Taylor SR, Bunce C, Longhurst H, Lynn W, Moots R, Stanford M, Tomkins-Netzer O, Yang D, Calder VL, Haskard DO (2015) Pegylated interferon-alpha-2b reduces corticosteroid requirement in patients with Behcet’s disease with upregulation of circulating regulatory T cells and reduction of Th17. Ann Rheum Dis 74(6):1138–1144. https://doi.org/10.1136/annrheumdis-2014-205571

    Article  CAS  PubMed  Google Scholar 

  63. Davatchi F, Shams H, Rezaipoor M, Sadeghi-Abdollahi B, Shahram F, Nadji A, Chams-Davatchi C, Akhlaghi M, Faezi T, Naderi N (2010) Rituximab in intractable ocular lesions of Behcet’s disease; randomized single-blind control study (pilot study). Int J Rheum Dis 13(3):246–252. https://doi.org/10.1111/j.1756-185X.2010.01546.x

    Article  PubMed  Google Scholar 

  64. Fabiani C, Vitale A, Emmi G, Lopalco G, Vannozzi L, Guerriero S, Gentileschi S, Bacherini D, Franceschini R, Frediani B, Galeazzi M, Iannone F, Tosi GM, Cantarini L (2017) Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behcet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):191–197. https://doi.org/10.1007/s10067-016-3506-4

    Article  PubMed  Google Scholar 

  65. Fabiani C, Vitale A, Emmi G, Vannozzi L, Lopalco G, Guerriero S, Orlando I, Franceschini R, Bacherini D, Cimino L, Soriano A, Frediani B, Galeazzi M, Iannone F, Tosi GM, Salvarani C, Cantarini L (2017) Efficacy and safety of adalimumab in Behcet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36(1):183–189. https://doi.org/10.1007/s10067-016-3480-x

    Article  PubMed  Google Scholar 

  66. Lopalco G, Rigante D, Giannini M, Galeazzi M, Lapadula G, Iannone F, Cantarini L (2016) Safety profile of anakinra in the management of rheumatologic, metabolic and autoinflammatory disorders. Clin Exp Rheumatol 34(3):531–538

    PubMed  Google Scholar 

  67. Gjoni M, Ozguler Y, Karatemiz G, Ugurlu S, Hatemi G, Melikoglu M, Fresko I, Ozyazgan Y, Seyahi E (2007) Behçet sendromunda anti IL-1 tedavisi: tek merkez deneyimi. RAED J 9(Suppl):S64. https://doi.org/10.2399/raed.17.S001017

    Article  Google Scholar 

  68. Papo M, Bielefeld P, Vallet H, Seve P, Wechsler B, Cacoub P, Le Hoang P, Papo T, Bodaghi B, Saadoun D (2014) Tocilizumab in severe and refractory non-infectious uveitis. Clin Exp Rheumatol 32(4 Suppl 84):S75–79

    PubMed  Google Scholar 

  69. Santos-Gomez M, Calvo-Rio V, Blanco R, Beltran E, Mesquida M, Adan A, Cordero-Coma M, Garcia-Aparicio AM, Valls Pascual E, Martinez-Costa L, Hernandez MV, Hernandez Garfella M, Gonzalez-Vela MC, Pina T, Palmou-Fontana N, Loricera J, Hernandez JL, Gonzalez-Gay MA (2016) The effect of biologic therapy different from infliximab or adalimumab in patients with refractory uveitis due to Behcet’s disease: results of a multicentre open-label study. Clin Exp Rheumatol 34(6 Suppl 102):S34–S40

    PubMed  Google Scholar 

  70. Alokaily F, Al Saati A, Jawad A (2017) Successful treatment of Behcet’s uveitis with Tocilizumab. Saudi J Ophthalmol 31(1):42–44. https://doi.org/10.1016/j.sjopt.2016.12.004

    Article  CAS  PubMed  Google Scholar 

  71. Eser Ozturk H, Oray M, Tugal-Tutkun I (2017) Tocilizumab for the Treatment of Behcet Uveitis that Failed Interferon Alpha and Anti-Tumor Necrosis Factor-Alpha Therapy. Ocul Immunol Inflamm. https://doi.org/10.1080/09273948.2017.1355471

  72. Fabiani C, Sota J, Rigante D, Vitale A, Emmi G, Vannozzi L, Franceschini R, Bacherini D, Frediani B, Galeazzi M, Tosi GM, Cantarini L (2017) Rapid and sustained efficacy of golimumab in the treatment of multirefractory uveitis associated with Behcet’s disease. Ocul Immunol Inflamm. https://doi.org/10.1080/09273948.2017.1351573

  73. Ozguler Y, Hatemi G, Cetinkaya F, Tascilar K, Ugurlu S, Seyahi E, Yazici H (2018) Interferon-alpha for the management of lower extremity deep vein thrombosis in Behcet’s syndrome: a case series. Ann Rheum Dis 77:1496

    Google Scholar 

  74. Seyahi E, Cakmak OS, Tutar B, Arslan C, Dikici AS, Sut N, Kantarci F, Tuzun H, Melikoglu M, Yazici H (2015) Clinical and ultrasonographic evaluation of lower-extremity vein thrombosis in Behcet syndrome: an observational study. Medicine (Baltimore) 94(44):e1899. https://doi.org/10.1097/MD.0000000000001899

    Article  Google Scholar 

  75. Alibaz-Oner F, Aldag B, Aldag M, Unal AU, Mutis A, Toptas T, Ergun T, Direskeneli H (2016) Post-thrombotic syndrome and venous disease-specific quality of life in patients with vascular Behcet’s disease. J Vasc Surg Venous Lymphat Disord 4(3):301–306. https://doi.org/10.1016/j.jvsv.2016.01.003

    Article  PubMed  Google Scholar 

  76. Emmi G, Vitale A, Silvestri E, Boddi M, Becatti M, Fiorillo C, Fabiani C, Frediani B, Emmi L, Di Scala G, Goldoni M, Bettiol A, Vaglio A, Cantarini L, Prisco D (2018) Adalimumab-based treatment versus disease-modifying antirheumatic drugs for venous thrombosis in Behcet’s syndrome: a retrospective study of seventy patients with vascular involvement. Arthritis Rheumatol. https://doi.org/10.1002/art.40531

  77. Seyahi E, Caglar E, Ugurlu S, Kantarci F, Hamuryudan V, Sonsuz A, Melikoglu M, Yurdakul S, Yazici H (2015) An outcome survey of 43 patients with Budd-Chiari syndrome due to Behcet’s syndrome followed up at a single, dedicated center. Semin Arthritis Rheum 44(5):602–609. https://doi.org/10.1016/j.semarthrit.2014.10.014

    Article  PubMed  Google Scholar 

  78. Desbois AC, Biard L, Addimanda O, Lambert M, Hachulla E, Launay D, Ackermann F, Perard L, Hot A, Maurier F, Mausservey C, Bernard F, Noel N, Alric L, Mirault T, Cohen F, Boussouar S, Resche-Rigon M, Cacoub P, Saadoun D (2018) Efficacy of anti-TNF alpha in severe and refractory major vessel involvement of Behcet’s disease: a multicenter observational study of 18 patients. Clin Immunol 197:54–59. https://doi.org/10.1016/j.clim.2018.08.004

    Article  CAS  PubMed  Google Scholar 

  79. Seyahi E (2016) Behcet’s disease: how to diagnose and treat vascular involvement. Best Pract Res Clin Rheumatol 30(2):279–295. https://doi.org/10.1016/j.berh.2016.08.002

    Article  PubMed  Google Scholar 

  80. Saba D, Saricaoglu H, Bayram AS, Erdogan C, Dilek K, Gebitekin C, Ozkan H, Ozer ZG (2003) Arterial lesions in Behcet’s disease. Vasa 32(2):75–81. https://doi.org/10.1024/0301-1526.32.2.75

    Article  CAS  PubMed  Google Scholar 

  81. Hamuryudan V, Yurdakul S, Moral F, Numan F, Tuzun H, Tuzuner N, Mat C, Tuzun Y, Ozyazgan Y, Yazici H (1994) Pulmonary arterial aneurysms in Behcet’s syndrome: a report of 24 cases. Br J Rheumatol 33(1):48–51

    Article  CAS  PubMed  Google Scholar 

  82. Seyahi E, Melikoglu M, Akman C, Hamuryudan V, Ozer H, Hatemi G, Yurdakul S, Tuzun H, Oz B, Yazici H (2012) Pulmonary artery involvement and associated lung disease in Behcet disease: a series of 47 patients. Medicine (Baltimore) 91(1):35–48. https://doi.org/10.1097/MD.0b013e318242ff37

    Article  Google Scholar 

  83. Tuzun H, Seyahi E, Guzelant G, Oz B, Batur S, Demirhan O, Hamuryudan V (2018) Surgical treatment of pulmonary complications in Behcet’s syndrome. Semin Thorac Cardiovasc Surg. https://doi.org/10.1053/j.semtcvs.2018.07.008

  84. Yildizeli SO, Yanartas M, Tas S, Direskeneli H, Mutlu B, Ceyhan B, Yildizeli B (2018) Outcomes of patients with Behcet’s syndrome after pulmonary endarterectomy. Thorac Cardiovasc Surg 66(2):187–192. https://doi.org/10.1055/s-0037-1604411

    Article  PubMed  Google Scholar 

  85. Esatoglu SN, Seyahi E, Ugurlu S, Gulsen F, Akman C, Cantasdemir M, Numan F, Tuzun H, Melikoglu M, Yazici H, Hamuryudan V (2016) Bronchial artery enlargement may be the cause of recurrent haemoptysis in Behcet’s syndrome patients with pulmonary artery involvement during follow-up. Clin Exp Rheumatol 34(6 Suppl 102):92–96

    PubMed  Google Scholar 

  86. Uygunoglu U, Siva A (2018) Behcet’s syndrome and nervous system involvement. Curr Neurol Neurosci Rep 18(7):35. https://doi.org/10.1007/s11910-018-0843-5

    Article  PubMed  Google Scholar 

  87. Zeydan B, Uygunoglu U, Saip S, Demirci ON, Seyahi E, Ugurlu S, Hamuryudan V, Siva A, Kantarci OH (2016) Infliximab is a plausible alternative for neurologic complications of Behcet disease. Neurol Neuroimmunol Neuroinflamm 3(5):e258. https://doi.org/10.1212/NXI.0000000000000258

    Article  PubMed  PubMed Central  Google Scholar 

  88. Noel N, Bernard R, Wechsler B, Resche-Rigon M, Depaz R, Boutin D, Piette JC, Drier A, Dormont D, Cacoub P, Saadoun D (2014) Long-term outcome of neuro-Behcet’s disease. Arthritis Rheumatol 66(5):1306–1314. https://doi.org/10.1002/art.38351

    Article  PubMed  Google Scholar 

  89. Yoon DL, Kim YJ, Koo BS, Kim YG, Lee CK, Yoo B (2014) Neuro-behcet’s disease in South Korea: clinical characteristics and treatment response. Int J Rheum Dis 17(4):453–458. https://doi.org/10.1111/1756-185X.12265

    Article  PubMed  Google Scholar 

  90. Shugaiv E, Tuzun E, Mutlu M, Kiyat-Atamer A, Kurtuncu M, Akman-Demir G (2011) Mycophenolate mofetil as a novel immunosuppressant in the treatment of neuro-Behcet’s disease with parenchymal involvement: presentation of four cases. Clin Exp Rheumatol 29(4 Suppl 67):S64–67

    PubMed  Google Scholar 

  91. Addimanda O, Pipitone N, Pazzola G, Salvarani C (2015) Tocilizumab for severe refractory neuro-Behcet: three cases IL-6 blockade in neuro-Behcet. Semin Arthritis Rheum 44(4):472–475. https://doi.org/10.1016/j.semarthrit.2014.08.004

    Article  CAS  PubMed  Google Scholar 

  92. Urbaniak P, Hasler P, Kretzschmar S (2012) Refractory neuro-Behcet treated by tocilizumab: a case report. Clin Exp Rheumatol 30(3 Suppl 72):S73–75

    CAS  PubMed  Google Scholar 

  93. Tascilar K, Melikoglu M, Ugurlu S, Sut N, Caglar E, Yazici H (2014) Vascular involvement in Behcet’s syndrome: a retrospective analysis of associations and the time course. Rheumatology (Oxford) 53(11):2018–2022. https://doi.org/10.1093/rheumatology/keu233

    Article  CAS  Google Scholar 

  94. Saadoun D, Wechsler B, Resche-Rigon M, Trad S, Le Thi Huong D, Sbai A, Dormont D, Amoura Z, Cacoub P, Piette JC (2009) Cerebral venous thrombosis in Behcet’s disease. Arthritis Rheum 61(4):518–526. https://doi.org/10.1002/art.24393

    Article  CAS  PubMed  Google Scholar 

  95. Roriz M, Crassard I, Lechtman S, Saadoun D, Champion K, Wechsler B, Chabriat H, Sene D (2018) Can anticoagulation therapy in cerebral venous thrombosis associated with Behcet’s disease be stopped without relapse? Rev Neurol (Paris) 174(3):162–166. https://doi.org/10.1016/j.neurol.2017.06.021

    Article  CAS  Google Scholar 

  96. Park YE, Cheon JH (2018) Updated treatment strategies for intestinal Behcet’s disease. Korean J Intern Med 33(1):1–19. https://doi.org/10.3904/kjim.2017.377

    Article  CAS  PubMed  Google Scholar 

  97. Hatemi I, Hatemi G, Celik AF (2018) Gastrointestinal involvement in Behcet disease. Rheum Dis Clin North Am 44(1):45–64. https://doi.org/10.1016/j.rdc.2017.09.007

    Article  PubMed  Google Scholar 

  98. Hisamatsu T, Hayashida M (2017) Treatment and outcomes: medical and surgical treatment for intestinal Behcet’s disease. Intest Res 15(3):318–327. https://doi.org/10.5217/ir.2017.15.3.318

    Article  PubMed  PubMed Central  Google Scholar 

  99. Park J, Cheon JH, Park Y, Park SJ, Kim TI, Kim WH (2018) Efficacy and tolerability of methotrexate therapy for refractory intestinal Behcet’s disease: a single center experience. Intest Res 16(2):315–318. https://doi.org/10.5217/ir.2018.16.2.315

    Article  PubMed  PubMed Central  Google Scholar 

  100. Ma D, Zhang CJ, Wang RP, Wang L, Yang H (2014) Etanercept in the treatment of intestinal Behcet’s disease. Cell Biochem Biophys 69(3):735–739. https://doi.org/10.1007/s12013-014-9860-4

    Article  CAS  PubMed  Google Scholar 

  101. Hatemi I, Hatemi G, Pamuk ON, Erzin Y, Celik AF (2015) TNF-alpha antagonists and thalidomide for the management of gastrointestinal Behcet’s syndrome refractory to the conventional treatment modalities: a case series and review of the literature. Clin Exp Rheumatol 33(6 Suppl 94):S129–137

    PubMed  Google Scholar 

  102. Chen J, Chen S, He J (2017) A case of refractory intestinal Behcet’s disease treated with tocilizumab, a humanised anti-interleukin-6 receptor antibody. Clin Exp Rheumatol 35(6):116–118

    PubMed  Google Scholar 

  103. Esatoglu SN, Hatemi G, Salihoglu A, Hatemi I, Soysal T, Celik AF (2015) A reappraisal of the association between Behcet’s disease, myelodysplastic syndrome and the presence of trisomy 8: a systematic literature review. Clin Exp Rheumatol 33(6 Suppl 94):S145–151

    PubMed  Google Scholar 

  104. Soysal T, Salihoglu A, Esatoglu SN, Gulturk E, Eskazan AE, Hatemi G, Hatemi I, Ongoren Aydin S, Erzin YZ, Baslar Z, Tuzuner N, Ferhanoglu B, Celik AF (2014) Bone marrow transplantation for Behcet’s disease: a case report and systematic review of the literature. Rheumatology (Oxford) 53(6):1136–1141. https://doi.org/10.1093/rheumatology/ket479

    Article  CAS  Google Scholar 

  105. Beales IL (1998) Gastrointestinal involvement in Behcet’s syndrome. Am J Gastroenterol 93(12):2633. https://doi.org/10.1111/j.1572-0241.1998.02633.x

    Article  CAS  PubMed  Google Scholar 

  106. Cantarini L, Stromillo ML, Vitale A, Lopalco G, Emmi G, Silvestri E, Federico A, Galeazzi M, Iannone F, De Stefano N (2016) Efficacy and safety of intravenous immunoglobulin treatment in refractory Behcet’s disease with different organ involvement: a case series. Isr Med Assoc J 18(3–4):238–242

    PubMed  Google Scholar 

  107. Wechsler B, Sable-Fourtassou R, Bodaghi B, Huong DL, Cassoux N, Badelon I, Fain O, LeHoang P, Piette JC (2004) Infliximab in refractory uveitis due to Behcet’s disease. Clin Exp Rheumatol 22(4 Suppl 34):S14–16

    CAS  PubMed  Google Scholar 

  108. Seider N, Beiran I, Scharf J, Miller B (2001) Intravenous immunoglobulin therapy for resistant ocular Behcet’s disease. Br J Ophthalmol 85(11):1287–1288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Rewald E, Jaksic JC (1990) Behcet’s syndrome treated with high-dose intravenous IgG and low-dose aspirin. J R Soc Med 83(10):652–653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Shutty B, Garg KJ, Swender D, Chernin L, Tcheurekdjian H, Hostoffer R (2012) Optimal use of ivig in a patient with Behcet syndrome and common variable immunodeficiency. Ann Allergy Asthma Immunol 109(1):84. https://doi.org/10.1016/j.anai.2012.05.014

    Article  PubMed  Google Scholar 

  111. Capittini C, Emmi G, De Amici M, Aronico N, Scudeller L, Antoniazzi E, Di Stefano M, Tinelli C (2016) Longitudinal analysis of serum cytokines in a Behcet’s patient during 9 months of IVIG infusions: how does CXCL8 bridge the immune and neuroendocrine systems? Immunol Lett 180:79–80. https://doi.org/10.1016/j.imlet.2016.10.012

    Article  CAS  PubMed  Google Scholar 

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  1. Division of Rheumatology, Department of Internal Medicine, Cerrahpasa Medical School, Istanbul University-Cerrahpasa, 34098, Istanbul, Turkey

    Sinem Nihal Esatoglu & Gulen Hatemi

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Esatoglu, S.N., Hatemi, G. Update on the treatment of Behçet’s syndrome. Intern Emerg Med 14, 661–675 (2019). https://doi.org/10.1007/s11739-019-02035-1

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