Skip to main content
Top
Published in: Ophthalmology and Therapy 5/2023

Open Access 21-07-2023 | Uveitis | REVIEW

Shaping the Future of Behçet’s Uveitis Management: A Comprehensive Review of Efficacy, Challenges, and Prospects of Biologic Therapies

Authors: Biao Li, Haoran Li, Qun Huang, Yanlin Zheng

Published in: Ophthalmology and Therapy | Issue 5/2023

Login to get access

Abstract

Behçet’s uveitis (BU), a vision-threatening manifestation of Behçet’s disease, poses substantial management challenges due to its chronic, relapsing nature and potential for vision loss. This review explores the role of biologic therapies in the treatment of BU, providing a comprehensive overview of their effectiveness, drawbacks, and future possibilities. Traditionally, management has relied heavily on corticosteroids and conventional immunosuppressants. However, their long-term use is frequently associated with systemic side effects and insufficient control of ocular inflammation. Biologic therapies, particularly TNF-alpha inhibitors like infliximab and adalimumab, have emerged as effective alternatives, offering better disease control and a more favorable safety profile. We critically evaluated these agents, noting their clinical efficacy in reducing inflammatory flares and preserving visual acuity. Despite their benefits, several issues remain. Accessibility, cost, and lack of long-term safety data limit their widespread use. Additionally, individual variability in treatment response necessitates personalized therapeutic strategies. Recent research has shown promise in addressing these challenges, with the emergence of novel biologic agents and personalized medicine approaches. In summary, biologic therapies represent a paradigm shift in BU management, contributing to better patient outcomes. Yet, there are significant challenges to be overcome. As we move forward, continued research, development of novel biologic agents, and a precision medicine approach will shape the future landscape of BU treatment.
Literature
1.
go back to reference Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Altunbas HH, Urgancioglu M. Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol. 2004;138(3):373–80.CrossRefPubMed Tugal-Tutkun I, Onal S, Altan-Yaycioglu R, Altunbas HH, Urgancioglu M. Uveitis in Behçet disease: an analysis of 880 patients. Am J Ophthalmol. 2004;138(3):373–80.CrossRefPubMed
10.
go back to reference Sugita S, Kawazoe Y, Imai A, Yamada Y, Horie S, Mochizuki M. Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behcet’s disease. Arthritis Res Ther. 2012;14(3):R99.CrossRefPubMedPubMedCentral Sugita S, Kawazoe Y, Imai A, Yamada Y, Horie S, Mochizuki M. Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behcet’s disease. Arthritis Res Ther. 2012;14(3):R99.CrossRefPubMedPubMedCentral
20.
go back to reference Sakai T, Kanetaka A, Noro T, Tsuneoka H. Intraocular surgery in patients receiving infliximab therapy for Behçet disease. Jpn J Ophthalmol. 2010;54(4):360.CrossRefPubMed Sakai T, Kanetaka A, Noro T, Tsuneoka H. Intraocular surgery in patients receiving infliximab therapy for Behçet disease. Jpn J Ophthalmol. 2010;54(4):360.CrossRefPubMed
28.
go back to reference Ohno S, Nakamura S, Hori S, Shimakawa M, Kawashima H, Mochizuki M, et al. Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behcet’s disease with refractory uveoretinitis. J Rheumatol. 2004;31(7):1362–8.PubMed Ohno S, Nakamura S, Hori S, Shimakawa M, Kawashima H, Mochizuki M, et al. Efficacy, safety, and pharmacokinetics of multiple administration of infliximab in Behcet’s disease with refractory uveoretinitis. J Rheumatol. 2004;31(7):1362–8.PubMed
33.
go back to reference Tabbara KF, Al-Hemidan AI. Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease. Am J Ophthalmol. 2008;146(6):845-50.e1.CrossRefPubMed Tabbara KF, Al-Hemidan AI. Infliximab effects compared to conventional therapy in the management of retinal vasculitis in Behçet disease. Am J Ophthalmol. 2008;146(6):845-50.e1.CrossRefPubMed
35.
go back to reference Urruticoechea-Arana A, Cobo-Ibanez T, Villaverde-Garcia V, Santos Gomez M, Loza E, Vargas-Osorio K, et al. Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behcet’s disease associated uveitis: a systematic review. Rheumatol Int. 2019;39(1):47–58. https://doi.org/10.1007/s00296-018-4193-z.CrossRefPubMed Urruticoechea-Arana A, Cobo-Ibanez T, Villaverde-Garcia V, Santos Gomez M, Loza E, Vargas-Osorio K, et al. Efficacy and safety of biological therapy compared to synthetic immunomodulatory drugs or placebo in the treatment of Behcet’s disease associated uveitis: a systematic review. Rheumatol Int. 2019;39(1):47–58. https://​doi.​org/​10.​1007/​s00296-018-4193-z.CrossRefPubMed
36.
go back to reference Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients. Am J Ophthalmol. 2012;154(3):534-41.e1.CrossRefPubMed Markomichelakis N, Delicha E, Masselos S, Sfikakis PP. Intravitreal infliximab for sight-threatening relapsing uveitis in Behçet disease: a pilot study in 15 patients. Am J Ophthalmol. 2012;154(3):534-41.e1.CrossRefPubMed
44.
go back to reference Guzelant G, Ucar D, Esatoglu SN, Hatemi G, Ozyazgan Y, Yurdakul S, et al. Infliximab for uveitis of Behcet’s syndrome: a trend for earlier initiation. Clin Exp Rheumatol. 2017;35(Suppl 108):86–9.PubMed Guzelant G, Ucar D, Esatoglu SN, Hatemi G, Ozyazgan Y, Yurdakul S, et al. Infliximab for uveitis of Behcet’s syndrome: a trend for earlier initiation. Clin Exp Rheumatol. 2017;35(Suppl 108):86–9.PubMed
47.
go back to reference Cantarini L, Lopalco G, Caso F, Costa L, Iannone F, Lapadula G, et al. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet’s disease. Autoimmun Rev. 2015;14(1):1–9.CrossRefPubMed Cantarini L, Lopalco G, Caso F, Costa L, Iannone F, Lapadula G, et al. Effectiveness and tuberculosis-related safety profile of interleukin-1 blocking agents in the management of Behçet’s disease. Autoimmun Rev. 2015;14(1):1–9.CrossRefPubMed
48.
go back to reference Vallet H, Seve P, Biard L, Baptiste Fraison J, Bielefeld P, Perard L, et al. Infliximab versus adalimumab in the treatment of refractory inflammatory uveitis: a multicenter study from the French uveitis network. Arthrit Rheumatol. 2016;68(6):1522–30. https://doi.org/10.1002/art.39667.CrossRef Vallet H, Seve P, Biard L, Baptiste Fraison J, Bielefeld P, Perard L, et al. Infliximab versus adalimumab in the treatment of refractory inflammatory uveitis: a multicenter study from the French uveitis network. Arthrit Rheumatol. 2016;68(6):1522–30. https://​doi.​org/​10.​1002/​art.​39667.CrossRef
49.
go back to reference Gueudry J, LeHoang P, Bodaghi B. Anti-tumor necrosis factor-α agents in noninfectious uveitis. In: New treatments in noninfectious uveitis. Karger Publishers; 2012. p. 63–78.CrossRef Gueudry J, LeHoang P, Bodaghi B. Anti-tumor necrosis factor-α agents in noninfectious uveitis. In: New treatments in noninfectious uveitis. Karger Publishers; 2012. p. 63–78.CrossRef
51.
go back to reference Olivieri I, Leccese P, D’angelo S, Padula A, Nigro A, Palazzi C, et al. Efficacy of adalimumab in patients with Behçet’s disease unsuccessfully treated with infliximab. Clin Exp Rheumatol. 2011;29(4 Suppl 67):S54–7.PubMed Olivieri I, Leccese P, D’angelo S, Padula A, Nigro A, Palazzi C, et al. Efficacy of adalimumab in patients with Behçet’s disease unsuccessfully treated with infliximab. Clin Exp Rheumatol. 2011;29(4 Suppl 67):S54–7.PubMed
55.
go back to reference Perra D, Alba MA, Callejas JL, Mesquida M, Ríos-Fernández R, Adan A, et al. Adalimumab for the treatment of Behçet’s disease: experience in 19 patients. Rheumatology. 2012;51(10):1825–31.CrossRefPubMed Perra D, Alba MA, Callejas JL, Mesquida M, Ríos-Fernández R, Adan A, et al. Adalimumab for the treatment of Behçet’s disease: experience in 19 patients. Rheumatology. 2012;51(10):1825–31.CrossRefPubMed
57.
go back to reference Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375(10):932–43.CrossRefPubMed Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, et al. Adalimumab in patients with active noninfectious uveitis. N Engl J Med. 2016;375(10):932–43.CrossRefPubMed
58.
go back to reference Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, et al. 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 (Lond, Engl). 2016;388(10050):1183–92. https://doi.org/10.1016/s0140-6736(16)31339-3.CrossRef Nguyen QD, Merrill PT, Jaffe GJ, Dick AD, Kurup SK, Sheppard J, et al. 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 (Lond, Engl). 2016;388(10050):1183–92. https://​doi.​org/​10.​1016/​s0140-6736(16)31339-3.CrossRef
64.
go back to reference Bitossi A, Bettiol A, Silvestri E, Di Scala G, Bacherini D, Lopalco G, et al. Adalimumab accounts for long-term control of noninfectious uveitis also in the absence of concomitant DMARD treatment: a multicenter retrospective study. Mediat Inflamm. 2019;2019:1623847. https://doi.org/10.1155/2019/1623847.CrossRef Bitossi A, Bettiol A, Silvestri E, Di Scala G, Bacherini D, Lopalco G, et al. Adalimumab accounts for long-term control of noninfectious uveitis also in the absence of concomitant DMARD treatment: a multicenter retrospective study. Mediat Inflamm. 2019;2019:1623847. https://​doi.​org/​10.​1155/​2019/​1623847.CrossRef
67.
go back to reference Smolen J, Kay J, Landewé R, Matteson E, Gaylis N, Wollenhaupt J, et al. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160. Ann Rheum Dis. 2012;71(10):1671–9. https://doi.org/10.1136/annrheumdis-2011-200956.CrossRefPubMed Smolen J, Kay J, Landewé R, Matteson E, Gaylis N, Wollenhaupt J, et al. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160. Ann Rheum Dis. 2012;71(10):1671–9. https://​doi.​org/​10.​1136/​annrheumdis-2011-200956.CrossRefPubMed
69.
go back to reference Santos-Gomez M, Calvo-Rio V, Blanco R, Beltran E, Mesquida M, Adan A, et al. 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. 2016;34(6 Supplement 102):S34–40.PubMed Santos-Gomez M, Calvo-Rio V, Blanco R, Beltran E, Mesquida M, Adan A, et al. 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. 2016;34(6 Supplement 102):S34–40.PubMed
70.
go back to reference Vitale A, Emmi G, Lopalco G, Fabiani C, Gentileschi S, Silvestri E, et al. Long-term efficacy and safety of golimumab in the treatment of multirefractory Behçet’s disease. Clin Rheumatol. 2017;36(9):2063–9.CrossRefPubMed Vitale A, Emmi G, Lopalco G, Fabiani C, Gentileschi S, Silvestri E, et al. Long-term efficacy and safety of golimumab in the treatment of multirefractory Behçet’s disease. Clin Rheumatol. 2017;36(9):2063–9.CrossRefPubMed
73.
go back to reference Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul S, et al. Short-term trial of etanercept in Behcet’s disease: a double blind, placebo controlled study. J Rheumatol. 2005;32(1):98–105.PubMed Melikoglu M, Fresko I, Mat C, Ozyazgan Y, Gogus F, Yurdakul S, et al. Short-term trial of etanercept in Behcet’s disease: a double blind, placebo controlled study. J Rheumatol. 2005;32(1):98–105.PubMed
78.
go back to reference Reddy AK, Albini TA. A review of biologics for uveitis. Retin Today. 2015;1:54–6. Reddy AK, Albini TA. A review of biologics for uveitis. Retin Today. 2015;1:54–6.
83.
go back to reference Kötter I, Günaydin I, Zierhut M, Stübiger N. The use of interferon α in Behçet disease: review of the literature. In: Seminars in arthritis and rheumatism. Elsevier; 2004. p. 320–35. Kötter I, Günaydin I, Zierhut M, Stübiger N. The use of interferon α in Behçet disease: review of the literature. In: Seminars in arthritis and rheumatism. Elsevier; 2004. p. 320–35.
89.
go back to reference Kavandi H, Khabbazi A, Kolahi S, Hajialilo M, Shayan FK, Oliaei M. Long-term efficacy and safety of interferon α-2a therapy in severe refractory ophthalmic Behcet’s disease. Clin Rheumatol. 2016;35(11):2765–9.CrossRefPubMed Kavandi H, Khabbazi A, Kolahi S, Hajialilo M, Shayan FK, Oliaei M. Long-term efficacy and safety of interferon α-2a therapy in severe refractory ophthalmic Behcet’s disease. Clin Rheumatol. 2016;35(11):2765–9.CrossRefPubMed
93.
go back to reference Onal S, Kazokoglu H, Koc A, Akman M, Bavbek T, Direskeneli H, et al. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis. Arch Ophthalmol. 2011;129(3):288–94.CrossRefPubMed Onal S, Kazokoglu H, Koc A, Akman M, Bavbek T, Direskeneli H, et al. Long-term efficacy and safety of low-dose and dose-escalating interferon alfa-2a therapy in refractory Behçet uveitis. Arch Ophthalmol. 2011;129(3):288–94.CrossRefPubMed
94.
go back to reference Keskin Y, Seyahi E, Poyraz C, Ugurlu S, Ozyazgan Y, Yazici H. Interferon alfa-associated depression in patients with Behçet’s syndrome: a prospective controlled study. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S175.PubMed Keskin Y, Seyahi E, Poyraz C, Ugurlu S, Ozyazgan Y, Yazici H. Interferon alfa-associated depression in patients with Behçet’s syndrome: a prospective controlled study. Clin Exp Rheumatol. 2014;32(4 Suppl 84):S175.PubMed
97.
go back to reference Orlando I, Vitale A, Rigante D, Lopalco G, Fabiani C, Cantarini L. Long-term efficacy and safety of the interleukin-1 inhibitors anakinra and canakinumab in refractory Behcet disease uveitis and concomitant bladder papillary carcinoma. Intern Med J. 2017;47(9):1086–8. https://doi.org/10.1111/imj.13538.CrossRefPubMed Orlando I, Vitale A, Rigante D, Lopalco G, Fabiani C, Cantarini L. Long-term efficacy and safety of the interleukin-1 inhibitors anakinra and canakinumab in refractory Behcet disease uveitis and concomitant bladder papillary carcinoma. Intern Med J. 2017;47(9):1086–8. https://​doi.​org/​10.​1111/​imj.​13538.CrossRefPubMed
99.
go back to reference Emmi G, Silvestri E, Cameli A, Bacherini D, Vannozzi L, Squatrito D, et al. Anakinra for resistant Behçet uveitis: why not? Clin Exp Rheumatol. 2013;31:152–3.PubMed Emmi G, Silvestri E, Cameli A, Bacherini D, Vannozzi L, Squatrito D, et al. Anakinra for resistant Behçet uveitis: why not? Clin Exp Rheumatol. 2013;31:152–3.PubMed
102.
go back to reference Blech M, Peter D, Fischer P, Bauer MM, Hafner M, Zeeb M, et al. One target—two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1β. J Mol Biol. 2013;425(1):94–111.CrossRefPubMed Blech M, Peter D, Fischer P, Bauer MM, Hafner M, Zeeb M, et al. One target—two different binding modes: structural insights into gevokizumab and canakinumab interactions to interleukin-1β. J Mol Biol. 2013;425(1):94–111.CrossRefPubMed
103.
go back to reference Cantarini L, Vitale A, Borri M, Galeazzi M, Franceschini R. Successful use of canakinumab in a patient with resistant Behçet’s disease. Clin Exp Rheumatol. 2012;30(Suppl 72):S115.PubMed Cantarini L, Vitale A, Borri M, Galeazzi M, Franceschini R. Successful use of canakinumab in a patient with resistant Behçet’s disease. Clin Exp Rheumatol. 2012;30(Suppl 72):S115.PubMed
105.
go back to reference Kaly L, Rosner I. Tocilizumab—a novel therapy for non-organ-specific autoimmune diseases. Best Pract Res Clin Rheumatol. 2012;26(1):157–65.CrossRefPubMed Kaly L, Rosner I. Tocilizumab—a novel therapy for non-organ-specific autoimmune diseases. Best Pract Res Clin Rheumatol. 2012;26(1):157–65.CrossRefPubMed
106.
109.
go back to reference Tanaka T, Narazaki M, Ogata A, Kishimoto T. A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy. In: Seminars in immunology. Elsevier; 2014. p. 88–96. Tanaka T, Narazaki M, Ogata A, Kishimoto T. A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy. In: Seminars in immunology. Elsevier; 2014. p. 88–96.
111.
go back to reference Calvo-Río V, Santos-Gómez M, Calvo I, González-Fernández MI, López-Montesinos B, Mesquida M, et al. Anti–interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis-associated uveitis refractory to anti-tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthrit Rheumatol. 2017;69(3):668–75. https://doi.org/10.1002/art.39940.CrossRef Calvo-Río V, Santos-Gómez M, Calvo I, González-Fernández MI, López-Montesinos B, Mesquida M, et al. Anti–interleukin-6 receptor tocilizumab for severe juvenile idiopathic arthritis-associated uveitis refractory to anti-tumor necrosis factor therapy: a multicenter study of twenty-five patients. Arthrit Rheumatol. 2017;69(3):668–75. https://​doi.​org/​10.​1002/​art.​39940.CrossRef
Metadata
Title
Shaping the Future of Behçet’s Uveitis Management: A Comprehensive Review of Efficacy, Challenges, and Prospects of Biologic Therapies
Authors
Biao Li
Haoran Li
Qun Huang
Yanlin Zheng
Publication date
21-07-2023
Publisher
Springer Healthcare
Published in
Ophthalmology and Therapy / Issue 5/2023
Print ISSN: 2193-8245
Electronic ISSN: 2193-6528
DOI
https://doi.org/10.1007/s40123-023-00767-0

Other articles of this Issue 5/2023

Ophthalmology and Therapy 5/2023 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Webinar | 06-02-2024 | 20:00 (CET)

Mastering chronic pancreatitis pain: A multidisciplinary approach and practical solutions

Severe pain is the most common symptom of chronic pancreatitis. In this webinar, experts share the latest insights in pain management for chronic pancreatitis patients. Experts from a range of disciplines discuss pertinent cases and provide practical suggestions for use within clinical practice.

Sponsored by: Viatris

Developed by: Springer Healthcare