Skip to main content

Advertisement

SpringerLink
Log in

Efficacy and safety of adalimumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study

  • Original Article
  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Abstract

The study aim was to evaluate the efficacy of adalimumab (ADA) in a large series of Behçet’s disease (BD)-related uveitis. We performed a multicenter retrospective observational study including 40 selected patients (66 eyes) receiving ADA. Clinical data were retrospectively analyzed at baseline, at 3 and 12 months of treatment. Primary end point was reduction of ocular inflammatory flares. Secondary end points were improvement of best corrected visual acuity (BCVA), reduction of macular thickness measured by optical coherence tomography (OCT), reduction in the occurrence of vasculitis assessed by fluorescein angiography (FA), and evaluation of statistically significant differences between patients treated with ADA monotherapy and those undergoing ADA plus DMARDs and in patients firstly treated with ADA compared to patients previously administered with other biologics; ADA steroid sparing effect was also evaluated. During the first 12 months of ADA therapy, the number of flares significantly decreased from 200 flares/100 patients/year to 8.5 flares/100 patients/year (p < 0.0001). Similarly, BCVA improved if compared to baseline (7.4 ± 2.9 versus 8.5 ± 2.1, p = 0.03). OCT findings significantly improved showing a mean reduction of central macular thickness (CMT) of 27.27 ± 42.8 μm at the end of follow-up (p < 0.006). FA identified retinal vasculitis in 22 cases at baseline (55%), 8 (20%) cases after 3 months, and in only one (2.5%) case at 12-month follow-up. FA improvement was highly significant at 3- and 12-month follow-up if compared to baseline (p < 0.0001 and p = 0.006, respectively). ADA is highly effective and safe for the treatment of BD-related uveitis, providing a long-term control of ocular inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hatemi G, Seyahi E, Fresko I, Talarico R, Hamuryudan V (2014) Behçet’s syndrome: a critical digest of the 2013-2014 literature. Clin Exp Rheumatol 32:S112–S122

    PubMed  Google Scholar 

  2. Kitaichi N, Miyazaki A, Iwata D, Ohno S, Stanford MR, Chams H (2007) Ocular features of Behçet’s disease: an international collaborative study. Br J Ophthalmol 91:1579–1582. doi:10.1136/bjo.2007.123554

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Huseyin Altunbas H, Urgancioglu M (2004) Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol 138:373–380. doi:10.1016/j.ajo.2004.03.022

    Article  PubMed  Google Scholar 

  4. Kural-Seyahi E, Fresko I, Seyahi N, Ozyazgan Y, Mat C, Hamuryudan V et al (2003) The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center. Medicine (Baltimore) 82:60–76

    Article  Google Scholar 

  5. Wakefield D, Cunningham ET Jr, Tugal-Tutkun I, Khairallah M, Ohno S, Zierhut M (2012) Controversies in Behçet disease. Ocul Immunol Inflamm 20:6–11. doi:10.3109/09273948.2011.649153

    Article  PubMed  Google Scholar 

  6. Salvarani C, Pipitone N, Catanoso MG, Cimino L, Tumiati B, Macchioni P et al (2007) Epidemiology and clinical course of Behçet’s disease in the Reggio Emilia area of Northern Italy: a seventeen-year population-based study. Arthritis Rheumn 57:171–178. doi:10.1002/art.22500

    Article  Google Scholar 

  7. Talarico R, Cantarini L, d’Ascanio A, Figus M, Favati B, Baldini C et al (2016) Development of de novo major involvement during follow-up in Behçet’s syndrome. Clin Rheumatol 35:247–250. doi:10.1007/s10067-015-2906-1

    Article  PubMed  Google Scholar 

  8. Hatemi G, Silman A, Bang D, Bodaghi B, Chamberlain AM, Gul A et al (2008) EULAR recommendations for the management of Behçet disease. Ann Rheum Dis 67:1656–1662. doi:10.1136/ard.2007.080432

    Article  CAS  PubMed  Google Scholar 

  9. Barry RJ, Markandey B, Malhotra R, Knott H, Joji N, Mubin M et al (2014) Evidence-based practice in Behçet’s disease: identifying areas of unmet need for 2014. Orphanet J Rare Dis 9:16. doi:10.1186/1750-1172-9-16

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ozguler Y, Hatemi G (2016) Management of Behçet’s syndrome. Curr Opin Rheumatol 28:45–50. doi:10.1097/BOR.0000000000000231

    Article  CAS  PubMed  Google Scholar 

  11. Kavandi H, Khabbazi A, Kolahi S, Hajialilo M, Shayan FK, Oliaei M (2016) Long-term efficacy and safety of interferon α-2a therapy in severe refractory ophthalmic Behcet’s disease. Clin Rheumatol 35:2765–2769. doi:10.1007/s10067-016-3318-6

    Article  PubMed  Google Scholar 

  12. Fabiani C, Vitale A, Lopalco G, Iannone F, Frediani B, Cantarini L (2016) Different roles of TNF inhibitors in acute anterior uveitis associated with ankylosing spondylitis: state of the art. Clin Rheumatol 35:2631–2638. doi:10.1007/s10067-016-3426-3

    Article  PubMed  Google Scholar 

  13. Cordero-Coma M, Sobrin L (2015) Anti-tumor necrosis factor-α therapy in uveitis. Surv Ophthalmol 60:575–589. doi:10.1016/j.survophthal.2015.06.004

    Article  PubMed  Google Scholar 

  14. Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN (2014) Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology 121:785–96.e3. doi:10.1016/j.ophtha.2013.09.048

    Article  PubMed  Google Scholar 

  15. Fabiani C, Alió JL (2015) Local (topical and intraocular) therapy for ocular Adamantiades-Behçet’s disease. Curr Opin Ophthalmol 26:546–552. doi:10.1097/ICU.0000000000000210

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  17. Okada AA, Goto H, Ohno S, Mochizuki M, Ocular Behçet’s Disease Research Group Of Japan (2012) Ocular Behçet’s disease research Group of Japan. Multicenter study of infliximab for refractory uveoretinitis in Behcet disease. Arch Ophthalmol 130:592–598. doi:10.1001/archophthalmol.2011.2698

    Article  CAS  PubMed  Google Scholar 

  18. Sugita S, Yamada Y, Mochizuki M (2011) Relationship between serum infliximab levels and acute uveitis attacks in patients with Behçet disease. Br J Ophthalmol 95:549–552. doi:10.1136/bjo.2009.174888

    Article  PubMed  Google Scholar 

  19. Keino H, Okada AA, Watanabe T, Taki W (2011) Decreased ocular inflammatory attacks and background retinal and disc vascular leakage in patients with Behçet’s disease on infliximab therapy. Br J Ophthalmol 95:1245–1250. doi:10.1136/bjo.2010.194464

    Article  PubMed  Google Scholar 

  20. Tugal-Tutkun I, Mudun A, Urgancioglu M, Kamali S, Kasapoglu E, Inanc M et al (2005) Efficacy of infliximab in the treatment of uveitis that is resistant to treatment with the combination of azathioprine, cyclosporine, and corticosteroids in Behçet’s disease: an open-label trial. Arthritis Rheum 52:2478–2484. doi:10.1002/art.21231

    Article  CAS  PubMed  Google Scholar 

  21. Niccoli L, Nannini C, Benucci M, Chindamo D, Cassarà E, Salvarani C et al (2007) Long-term efficacy of infliximab in refractory posterior uveitis of Behçet’s disease: a 24-month follow-up study. Rheumatology (Oxford) 46:1161–1164. doi:10.1093/rheumatology/kem101

    Article  CAS  Google Scholar 

  22. Al Rashidi S, Al Fawaz A, Kangave D, Abu El-Asrar AM (2013) Long-term clinical outcomes in patients with refractory uveitis associated with Behçet disease treated with infliximab. Ocul Immunol Inflamm 21:468–474. doi:10.3109/09273948.2013.779727

    Article  CAS  PubMed  Google Scholar 

  23. Díaz-Llopis M, Salom D, Garcia-de-Vicuña C, Cordero-Coma M, Ortega G, Ortego N et al (2012) Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 119:1575–1581. doi:10.1016/j.ophtha.2012.02.018

    Article  PubMed  Google Scholar 

  24. Bawazeer A, Raffa LH, Nizamuddin SH (2010) Clinical experience with adalimumab in the treatment of ocular Behçet disease. Ocul Immunol Inflamm 18:226–232. doi:10.3109/09273948.2010.483314

    Article  CAS  PubMed  Google Scholar 

  25. Takase K, Ohno S, Ideguchi H, Uchio E, Takeno M, Ishigatsubo Y (2011) Successful switching to adalimumab in an infliximab-allergic patient with severe Behçet disease-related uveitis. Rheumatol Int 31:243–245. doi:10.1007/s00296-009-1178-y

    Article  CAS  PubMed  Google Scholar 

  26. Mushtaq B, Saeed T, Situnayake RD, Murray PI (2007) Adalimumab for sight-threatening uveitis in Behçet’s disease. Eye (Lond) 21:824–825. doi:10.1038/sj.eye.6702352

    Article  CAS  Google Scholar 

  27. Perra D, Alba MA, Callejas JL, Mesquida M, Ríos-Fernández R, Adán A et al (2012) Adalimumab for the treatment of Behçet’s disease: experience in 19 patients. Rheumatology (Oxford) 51:1825–1831. doi:10.1093/rheumatology/kes130

    Article  CAS  Google Scholar 

  28. Calvo Catalá J, Campos Fernández C, Rueda Cid A, González-Cruz Cervellera MI, Baixauli Rubio A, Pastor Cubillo MD (2011) Efficacy of adalimumab in Behçet’s disease. Description of 6 cases. Reumatol Clin 7:258–261. doi:10.1016/j.reuma.2010.10.003

    Article  PubMed  Google Scholar 

  29. Interlandi E, Leccese P, Olivieri I, Latanza L (2014) Adalimumab for treatment of severe Behçet’s uveitis: a retrospective long-term follow-up study. Clin Exp Rheumatol 32:S58–S62

    PubMed  Google Scholar 

  30. Leccese P, Latanza L, D’Angelo S, Padula A, Olivieri I (2011) Efficacy of switching to adalimumab in a patient with refractory uveitis of Behçet’s disease to infliximab. Clin Exp Rheumatol 29:S93

    PubMed  Google Scholar 

  31. Calvo-Río V, Blanco R, Beltrán E, Sánchez-Bursón J, Mesquida M, Adán A et al (2014) Anti-TNF-α therapy in patients with refractory uveitis due to Behçet’s disease: a 1-year follow-up study of 124 patients. Rheumatology (Oxford) 53:2223–2231. doi:10.1093/rheumatology/keu266

    Article  Google Scholar 

  32. Vallet H, Riviere S, Sanna A, Deroux A, Moulis G, Addimanda O et al (2015) Efficacy of anti-TNF alpha in severe and/or refractory Behçet’s disease: multicenter study of 124 patients. J Autoimmun 62:67–74. doi:10.1016/j.jaut.2015.06.005

    Article  CAS  PubMed  Google Scholar 

  33. Criteria for diagnosis of Behçet’s disease (1990) International study group for Behçet’s disease. Lancet 335:1078–1080

    Google Scholar 

  34. International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD) (2014) The international criteria for Behçet’s disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 28:338–347. doi:10.1111/jdv.12107

    Article  Google Scholar 

  35. Neves FS, Moraes JC, Kowalski SC, Goldenstein-Schainberg C, Lage LV, Gonçalves CR (2007) Cross-cultural adaptation of the Behçet’s disease current activity form (BDCAF) to Brazilian Portuguese language. Clin Rheumatol 26:1263–1267. doi:10.1007/s10067-006-0484-y

    Article  CAS  PubMed  Google Scholar 

  36. Cantini F, Niccoli L, Nannini C, Kaloudi O, Cassarà E, Susini M et al (2012) Efficacy of infliximab in refractory Behçet’s disease-associated and idiopathic posterior segment uveitis: a prospective, follow-up study of 50 patients. Biologics 6:5–1. doi:10.2147/BTT.S27343

    CAS  PubMed  Google Scholar 

  37. Schaap-Fogler M, Amer R, Friling R, Priel E, Kramer M (2014) Anti-TNF-α agents for refractory cystoid macular edema associated with noninfectious uveitis. Graefes Arch Clin Exp Ophthalmol 252:633–640. doi:10.1007/s00417-013-2552-8

    Article  CAS  PubMed  Google Scholar 

  38. Olivieri I, Leccese P, D’Angelo S, Padula A, Nigro A, Palazzi C et al (2011) Efficacy of adalimumab in patients with Behçet’s disease unsuccessfully treated with infliximab. Clin Exp Rheumatol 29:S54–S57

    PubMed  Google Scholar 

  39. Yazici H, Hatemi G (2012) Empiricism in managing Behçet’s syndrome. Clin Exp Rheumatol 30:S79

    Google Scholar 

  40. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of Uveitis Nomenclature (SUN) Working Group (2005) Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140:509–516

    Article  PubMed  Google Scholar 

  41. Khairallah M (2010) Are the Standardization of the Uveitis Nomenclature (SUN) Working Group criteria for codifying the site of inflammation appropriate for all uveitis problems? Limitations of the SUN Working Group classification. Ocul Immunol Inflamm 18:2–4. doi:10.3109/09273940903348835

    Article  PubMed  Google Scholar 

  42. Hatemi G, Merkel PA, Hamuryudan V, Boers M, Direskeneli H, Aydin SZ et al (2014) Outcome measures used in clinical trials for Behçet syndrome: a systematic review. J Rheumatol 41:599–612. doi:10.3899/jrheum.131249

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hatemi G, Ozguler Y, Direskeneli H, Mahr A, Gul A, Levi V et al (2015) Current status, goals, and research agenda for outcome measures development in Behçet syndrome: report from OMERACT 2014. J Rheumatol 42:2436–2441. doi:10.3899/jrheum.141147

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Humanitas Research Hospital, Rozzano, Milan, Italy

    Claudia Fabiani

  2. Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy

    Antonio Vitale, Ida Orlando, Bruno Frediani, Mauro Galeazzi & Luca Cantarini

  3. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Giacomo Emmi

  4. Department of Surgery and Translational Medicine, Eye Clinic, University of Florence, Florence, Italy

    Lorenzo Vannozzi & Daniela Bacherini

  5. Interdisciplinary Department of Medicine, Rheumatology Unit, University of Bari, Bari, Italy

    Giuseppe Lopalco & Florenzo Iannone

  6. Department of Ophthalmology and Otolaryngology, Bari University, Bari, Italy

    Silvana Guerriero

  7. Ophthalmology and Neurosurgery Department, University of Siena, Siena, Italy

    Rossella Franceschini & Gian Marco Tosi

  8. Department of Ophthalmology, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy

    Luca Cimino

  9. Department of Rheumatology, Arcispedale Santa Maria Nuova IRCCS, Reggio Emilia, Italy

    Alessandra Soriano & Carlo Salvarani

Authors
  1. Claudia Fabiani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Vitale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giacomo Emmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lorenzo Vannozzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giuseppe Lopalco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Silvana Guerriero
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ida Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rossella Franceschini
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Daniela Bacherini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Luca Cimino
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Alessandra Soriano
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Bruno Frediani
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Mauro Galeazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Florenzo Iannone
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Gian Marco Tosi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Carlo Salvarani
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Luca Cantarini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claudia Fabiani.

Ethics declarations

Disclosures

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fabiani, C., Vitale, A., Emmi, G. et al. Efficacy and safety of adalimumab in Behçet’s disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 36, 183–189 (2017). https://doi.org/10.1007/s10067-016-3480-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10067-016-3480-x

Keywords

Search

Navigation