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Klin Monbl Augenheilkd 2022; 239(05): 686-694
DOI: 10.1055/a-1737-4425
DOI: 10.1055/a-1737-4425
Übersicht
Biologics in the Treatment of Uveitis
Article in several languages: deutsch | English
Abstract
Goal To provide an overview of biologics that are used to treat noninfectious uveitis, including their different targets, modes of actions, and indications.
Material and Methods A review of recent and well-established literature was used to present the biochemical and pathophysiological background of biologics and to provide an account of evidence-based decision making for their use, not only in noninfectious uveitis in general, but with special regard to indications for their use in particular types of uveitis.
Results Extensive clinical data for adalimumab shows that it is currently the only approved biologic for the treatment of uveitis. However, there is sufficient evidence to argue that many other biologics, notably TNF-α inhibitors, certain Interleukin inhibitors, Interferons, and B cell and T cell inhibitors, are also suitable for use in uveitis.
Conclusions Biologics have revolutionized the treatment of noninfectious uveitis and are now considered indispensable. They are used in cases of insufficient response to or intolerance of conventional immunosuppressive agents. However, they can also be indicated as a first-line therapy for certain types of uveitis (e.g., Behçetʼs disease). TNF-α inhibitors are the most commonly used biologics in the treatment of uveitis.
Publication History
Received: 26 November 2021
Accepted: 06 January 2022
Article published online:
14 April 2022
© 2022. Thieme. All rights reserved.
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References/Literatur
- 1 Verband Forschender Arzneimittelhersteller e. V.. Übersicht über zentralisiert in der EU zugelassene Biosimilars. 18.11.2021 Im Internet (Stand: 26.11.2021): https://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/biosimilars-uebersicht
- 2 SwissDocu. Monoklonale Antikörper: Verschlüsselte Nomenklatur. 04.11.2020 Im Internet (Stand: 26.11.2021): https://www.swissdocu.ch/de/news/103-pharmazie/1148-monoklonale-antikoerper-verschluesselte-nomenklatur
- 3 Balamurugan S, Das D, Hasanreisoglu M. et al. Interleukins and cytokine biomarkers in uveitis. Indian J Ophthalmol 2020; 68: 1750-1763 DOI: 10.4103/ijo.IJO_564_20.
- 4 Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014; 6: a016295 DOI: 10.1101/cshperspect.a016295.
- 5 Babon JJ, Varghese LN, Nicola NA. Inhibition of IL-6 family cytokines by SOCS3. Semin Immunol 2014; 26: 13-19 DOI: 10.1016/j.smim.2013.12.004.
- 6 Eulenfeld R, Dittrich A, Khouri C. et al. Interleukin-6 signalling: more than Jaks and STATs. Eur J Cell Biol 2012; 91: 486-495 DOI: 10.1016/j.ejcb.2011.09.010.
- 7 Abu El-Asrar AM, Berghmans N, Al-Obeidan SA. et al. The Cytokine Interleukin-6 and the Chemokines CCL20 and CXCL13 Are Novel Biomarkers of Specific Endogenous Uveitic Entities. Invest Ophthalmol Vis Sci 2016; 57: 4606-4613 DOI: 10.1167/iovs.16-19758.
- 8 Chen W, Zhao B, Jiang R. et al. Cytokine Expression Profile in Aqueous Humor and Sera of Patients with Acute Anterior Uveitis. Curr Mol Med 2015; 15: 543-549 DOI: 10.2174/1566524015666150731100012.
- 9 de Visser L, de Boer JH, Rijkers GT. et al. Cytokines and Chemokines Involved in Acute Retinal Necrosis. Invest Ophthalmol Vis Sci 2017; 58: 2139-2151 DOI: 10.1167/iovs.16-20799.
- 10 Yoshimura T, Sonoda KH, Ohguro N. et al. Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis. Rheumatology (Oxford) 2009; 48: 347-354 DOI: 10.1093/rheumatology/ken489.
- 11 Weinstein JE, Pepple KL. Cytokines in uveitis. Curr Opin Ophthalmol 2018; 29: 267-274 DOI: 10.1097/ICU.0000000000000466.
- 12 Kuiper JJ, Mutis T, de Jager W. et al. Intraocular interleukin-17 and proinflammatory cytokines in HLA-A29-associated birdshot chorioretinopathy. Am J Ophthalmol 2011; 152: 177-182.e1 DOI: 10.1016/j.ajo.2011.01.031.
- 13 El-Asrar AM, Struyf S, Kangave D. et al. Cytokine profiles in aqueous humor of patients with different clinical entities of endogenous uveitis. Clin Immunol 2011; 139: 177-184 DOI: 10.1016/j.clim.2011.01.014.
- 14 Jawad S, Liu B, Agron E. et al. Elevated serum levels of interleukin-17A in uveitis patients. Ocul Immunol Inflamm 2013; 21: 434-439 DOI: 10.3109/09273948.2013.815786.
- 15 Na SY, Park MJ, Park S. et al. Up-regulation of Th17 and related cytokines in Behcetʼs disease corresponding to disease activity. Clin Exp Rheumatol 2013; 31: 32-40
- 16 Dick AD, Duncan L, Hale G. et al. Neutralizing TNF-alpha activity modulates T-cell phenotype and function in experimental autoimmune uveoretinitis. J Autoimmun 1998; 11: 255-264 DOI: 10.1006/jaut.1998.0197.
- 17 Raveney BJ, Copland DA, Dick AD. et al. TNFR1-dependent regulation of myeloid cell function in experimental autoimmune uveoretinitis. J Immunol 2009; 183: 2321-2329 DOI: 10.4049/jimmunol.0901340.
- 18 Valentincic NV, de Groot-Mijnes JD, Kraut A. et al. Intraocular and serum cytokine profiles in patients with intermediate uveitis. Mol Vis 2011; 17: 2003-2010
- 19 Gillies MC, Su T. Interferon-alpha 2b enhances barrier function of bovine retinal microvascular endothelium in vitro. Microvasc Res 1995; 49: 277-288 DOI: 10.1006/mvre.1995.1024.
- 20 Jaffe GJ, Dick AD, Brezin AP. et al. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med 2016; 375: 932-943 DOI: 10.1056/NEJMoa1509852.
- 21 Nguyen QD, Merrill PT, Jaffe GJ. 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 2016; 388: 1183-1192 DOI: 10.1016/S0140-6736(16)31339-3.
- 22 Suhler EB, Adan A, Brezin AP. et al. Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III. Ophthalmology 2018; 125: 1075-1087 DOI: 10.1016/j.ophtha.2017.12.039.
- 23 Ramanan AV, Dick AD, Benton D. et al. A randomised controlled trial of the clinical effectiveness, safety and cost-effectiveness of adalimumab in combination with methotrexate for the treatment of juvenile idiopathic arthritis associated uveitis (SYCAMORE Trial). Trials 2014; 15: 14 DOI: 10.1186/1745-6215-15-14.
- 24 Quartier P, Baptiste A, Despert V. et al. ADJUVITE: a double-blind, randomised, placebo-controlled trial of adalimumab in early onset, chronic, juvenile idiopathic arthritis-associated anterior uveitis. Ann Rheum Dis 2018; 77: 1003-1011 DOI: 10.1136/annrheumdis-2017-212089.
- 25 Suhler EB, Lowder CY, Goldstein DA. et al. Adalimumab therapy for refractory uveitis: results of a multicentre, open-label, prospective trial. Br J Ophthalmol 2013; 97: 481-486 DOI: 10.1136/bjophthalmol-2012-302292.
- 26 Díaz-Llopis M, Salom D, Garcia-de-Vicuñna C. et al. Treatment of refractory uveitis with adalimumab: a prospective multicenter study of 131 patients. Ophthalmology 2012; 119: 1575-1581 DOI: 10.1016/j.ophtha.2012.02.018.
- 27 Rudwaleit M, Rodevand E, Holck P. et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis 2009; 68: 696-701 DOI: 10.1136/ard.2008.092585.
- 28 van Denderen JC, Visman IM, Nurmohamed MT. et al. Adalimumab significantly reduces the recurrence rate of anterior uveitis in patients with ankylosing spondylitis. J Rheumatol 2014; 41: 1843-1848 DOI: 10.3899/jrheum.131289.
- 29 van der Heijde D, Ramiro S, Landewe R. et al. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 2017; 76: 978-991 DOI: 10.1136/annrheumdis-2016-210770.
- 30 Ward MM, Deodhar A, Akl EA. et al. American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis Rheumatol 2016; 68: 282-298 DOI: 10.1002/art.39298.
- 31 Gossec L, Baraliakos X, Kerschbaumer A. et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020; 79: 700-712 DOI: 10.1136/annrheumdis-2020-217159.
- 32 Coates LC, FitzGerald O, Merola JF. et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis/Outcome Measures in Rheumatology Consensus-Based Recommendations and Research Agenda for Use of Composite Measures and Treatment Targets in Psoriatic Arthritis. Arthritis Rheumatol 2018; 70: 345-355 DOI: 10.1002/art.40391.
- 33 Mushtaq B, Saeed T, Situnayake RD. et al. Adalimumab for sight-threatening uveitis in Behcetʼs disease. Eye (Lond) 2007; 21: 824-825 DOI: 10.1038/sj.eye.6702352.
- 34 Bawazeer A, Raffa LH, Nizamuddin SH. Clinical experience with adalimumab in the treatment of ocular Behcet disease. Ocul Immunol Inflamm 2010; 18: 226-232 DOI: 10.3109/09273948.2010.483314.
- 35 Levy-Clarke G, Jabs DA, Read RW. et al. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology 2014; 121: 785-796.e3 DOI: 10.1016/j.ophtha.2013.09.048.
- 36 Martel JN, Esterberg E, Nagpal A. et al. Infliximab and adalimumab for uveitis. Ocul Immunol Inflamm 2012; 20: 18-26 DOI: 10.3109/09273948.2011.633205.
- 37 Vallet H, Seve P, Biard L. et al. Infliximab Versus Adalimumab in the Treatment of Refractory Inflammatory Uveitis: A Multicenter Study From the French Uveitis Network. Arthritis Rheumatol 2016; 68: 1522-1530 DOI: 10.1002/art.39667.
- 38 Suhler EB, Smith JR, Wertheim MS. et al. A prospective trial of infliximab therapy for refractory uveitis: preliminary safety and efficacy outcomes. Arch Ophthalmol 2005; 123: 903-912 DOI: 10.1001/archopht.123.7.903.
- 39 Yamada Y, Sugita S, Tanaka H. et al. Timing of recurrent uveitis in patients with Behcetʼs disease receiving infliximab treatment. Br J Ophthalmol 2011; 95: 205-208 DOI: 10.1136/bjo.2009.168856.
- 40 Takeuchi M, Kezuka T, Sugita S. et al. Evaluation of the long-term efficacy and safety of infliximab treatment for uveitis in Behcetʼs disease: a multicenter study. Ophthalmology 2014; 121: 1877-1884 DOI: 10.1016/j.ophtha.2014.04.042.
- 41 Suhler EB, Smith JR, Giles TR. et al. Infliximab therapy for refractory uveitis: 2-year results of a prospective trial. Arch Ophthalmol 2009; 127: 819-822 DOI: 10.1001/archophthalmol.2009.141.
- 42 Dick AD, Rosenbaum JT, Al-Dhibi HA. et al. Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis: Fundamentals Of Care for UveitiS (FOCUS) Initiative. Ophthalmology 2018; 125: 757-773 DOI: 10.1016/j.ophtha.2017.11.017.
- 43 Tosi GM, Sota J, Vitale A. et al. Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis. Clin Exp Rheumatol 2019; 37: 680-683
- 44 Prieto-Pena D, Calderon-Goercke M, Adan A. et al. Efficacy and safety of certolizumab pegol in pregnant women with uveitis. Recommendations on the management with immunosuppressive and biologic therapies in uveitis during pregnancy. Clin Exp Rheumatol 2021; 39: 105-114
- 45 Atiqi S, Hooijberg F, Loeff FC. et al. Immunogenicity of TNF-Inhibitors. Front Immunol 2020; 11: 312 DOI: 10.3389/fimmu.2020.00312.
- 46 Fabiani C, Vitale A, Emmi G. et al. Interleukin (IL)-1 inhibition with anakinra and canakinumab in Behcetʼs disease-related uveitis: a multicenter retrospective observational study. Clin Rheumatol 2017; 36: 191-197 DOI: 10.1007/s10067-016-3506-4.
- 47 Brambilla A, Caputo R, Cimaz R. et al. Canakinumab for Childhood Sight-threatening Refractory Uveitis: A Case Series. J Rheumatol 2016; 43: 1445-1447 DOI: 10.3899/jrheum.160064.
- 48 Tugal-Tutkun I, Pavesio C, De Cordoue A. et al. Use of Gevokizumab in Patients with Behcetʼs Disease Uveitis: An International, Randomized, Double-Masked, Placebo-Controlled Study and Open-Label Extension Study. Ocul Immunol Inflamm 2018; 26: 1023-1033
- 49 Papo M, Bielefeld P, Vallet H. et al. Tocilizumab in severe and refractory non-infectious uveitis. Clin Exp Rheumatol 2014; 32 (4 Suppl. 84): S75-S79
- 50 Mesquida M, Molins B, Llorenc V. et al. Targeting interleukin-6 in autoimmune uveitis. Autoimmun Rev 2017; 16: 1079-1089 DOI: 10.1016/j.autrev.2017.08.002.
- 51 Deuter CME, Zierhut M, Igney-Oertel A. et al. Tocilizumab in Uveitic Macular Edema Refractory to Previous Immunomodulatory Treatment. Ocul Immunol Inflamm 2017; 25: 215-220 DOI: 10.3109/09273948.2015.1099680.
- 52 Mesquida M, Molins B, Llorenc V. et al. Twenty-Four Month Follow-up of Tocilizumab Therapy for Refractory Uveitis-Related Macular Edema. Retina 2018; 38: 1361-1370 DOI: 10.1097/IAE.0000000000001690.
- 53 Sepah YJ, Sadiq MA, Chu DS. et al. Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis. Am J Ophthalmol 2017; 183: 71-80 DOI: 10.1016/j.ajo.2017.08.019.
- 54 Calvo-Rio V, Santos-Gomez M, Calvo I. 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. Arthritis Rheumatol 2017; 69: 668-675 DOI: 10.1002/art.39940.
- 55 Atienza-Mateo B, Calvo-Rio V, Beltran E. et al. Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behcetʼs disease: multicentre retrospective study. Rheumatology (Oxford) 2018; 57: 856-864 DOI: 10.1093/rheumatology/kex480.
- 56 Dick AD, Tugal-Tutkun I, Foster S. et al. Secukinumab in the treatment of noninfectious uveitis: results of three randomized, controlled clinical trials. Ophthalmology 2013; 120: 777-787 DOI: 10.1016/j.ophtha.2012.09.040.
- 57 Letko E, Yeh S, Foster CS. et al. Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy. Ophthalmology 2015; 122: 939-948 DOI: 10.1016/j.ophtha.2014.12.033.
- 58 Miserocchi E, Giuffre C, Caporali R. et al. Secukinumab in HLA-B27 associated uveitis. Clin Exp Ophthalmol 2021; 49: 388-389 DOI: 10.1111/ceo.13922.
- 59 Suhler EB, Lim LL, Beardsley RM. et al. Rituximab therapy for refractory scleritis: results of a phase I/II dose-ranging, randomized, clinical trial. Ophthalmology 2014; 121: 1885-1891 DOI: 10.1016/j.ophtha.2014.04.044.
- 60 Ahmed A, Foster CS. Cyclophosphamide or Rituximab Treatment of Scleritis and Uveitis for Patients with Granulomatosis with Polyangiitis. Ophthalmic Res 2019; 61: 44-50 DOI: 10.1159/000486791.
- 61 Miserocchi E, Modorati G, Berchicci L. et al. Long-term treatment with rituximab in severe juvenile idiopathic arthritis-associated uveitis. Br J Ophthalmol 2016; 100: 782-786 DOI: 10.1136/bjophthalmol-2015-306790.
- 62 Davatchi F, Shams H, Rezaipoor M. et al. Rituximab in intractable ocular lesions of Behcetʼs disease; randomized single-blind control study (pilot study). Int J Rheum Dis 2010; 13: 246-252 DOI: 10.1111/j.1756-185X.2010.01546.x.
- 63 Tappeiner C, Miserocchi E, Bodaghi B. et al. Abatacept in the treatment of severe, longstanding, and refractory uveitis associated with juvenile idiopathic arthritis. J Rheumatol 2015; 42: 706-711 DOI: 10.3899/jrheum.140410.
- 64 Deuter C, Stubiger N, Zierhut M. Interferon-alpha therapy in noninfectious uveitis. Dev Ophthalmol 2012; 51: 90-97 DOI: 10.1159/000336324.
- 65 Kotter I, Zierhut M, Eckstein AK. et al. Human recombinant interferon alfa-2a for the treatment of Behcetʼs disease with sight threatening posterior or panuveitis. Br J Ophthalmol 2003; 87: 423-431 DOI: 10.1136/bjo.87.4.423.
- 66 Deuter CM, Zierhut M, Mohle A. et al. Long-term remission after cessation of interferon-alpha treatment in patients with severe uveitis due to Behcetʼs disease. Arthritis Rheum 2010; 62: 2796-2805 DOI: 10.1002/art.27581.
- 67 Deuter CM, Kotter I, Gunaydin I. et al. Efficacy and tolerability of interferon alpha treatment in patients with chronic cystoid macular oedema due to non-infectious uveitis. Br J Ophthalmol 2009; 93: 906-913 DOI: 10.1136/bjo.2008.153874.
- 68 Dimopoulos S, Deuter CME, Blumenstock G. et al. Interferon Alpha for Refractory Pseudophakic Cystoid Macular Edema (Irvine-Gass Syndrome). Ocul Immunol Inflamm 2020; 28: 315-321 DOI: 10.1080/09273948.2019.1585883.
- 69 Deuter CM, Gelisken F, Stubiger N. et al. Successful treatment of chronic pseudophakic macular edema (Irvine-Gass syndrome) with interferon alpha: a report of three cases. Ocul Immunol Inflamm 2011; 19: 216-218 DOI: 10.3109/09273948.2011.562341.
- 70 Becker MD, Heiligenhaus A, Hudde T. et al. Interferon as a treatment for uveitis associated with multiple sclerosis. Br J Ophthalmol 2005; 89: 1254-1257 DOI: 10.1136/bjo.2004.061119.
- 71 Mackensen F, Jakob E, Springer C. et al. Interferon versus methotrexate in intermediate uveitis with macular edema: results of a randomized controlled clinical trial. Am J Ophthalmol 2013; 156: 478-486.e1 DOI: 10.1016/j.ajo.2013.05.002.