Klin Monbl Augenheilkd 2022; 239(05): 686-694
DOI: 10.1055/a-1737-4425
Übersicht

Therapie der Uveitis mit Biologika

Article in several languages: deutsch | English
Vita Louisa Sophie Dingerkus
1   Department für Augenheilkunde, Stadtspital Zürich, Zürich, Schweiz
,
Matthias Dieter Becker
1   Department für Augenheilkunde, Stadtspital Zürich, Zürich, Schweiz
2   Department für Augenheilkunde, Universitätsklinikum Heidelberg, Deutschland
,
Deshka Doycheva
3   Department für Augenheilkunde, Universitätsklinikum Tübingen, Deutschland
› Author Affiliations

Zusammenfassung

Zielsetzung Ziel dieser Zusammenfassung ist das Vermitteln einer Übersicht zu den verschiedenen Ansatzpunkten, Wirkmechanismen und Indikationen diverser Biologika, die bei der Therapie der nichtinfektiösen Uveitis zum Einsatz kommen.

Material und Methoden Etablierte sowie aktuelle Literatur wurden herangezogen, um die biochemischen und pathophysiologischen Grundlagen sowie eine evidenzbasierte Empfehlung zum Therapieeinsatz verschiedener Biologika bei nichtinfektiöser Uveitis allgemein und bei speziellen Uveitisentitäten darzulegen.

Ergebnisse Für viele Biologika, hier nennenswert TNF-α-Inhibitoren, einige Interleukininhibitoren, Interferone sowie B- und T-Zell-Inhibitoren, liegen mittlerweile gute Daten vor, was ihren Einsatz in der Uveitistherapie mehr als rechtfertigt. Dies trifft insbesondere für den TNF-α-Inhibitor Adalimumab zu, welcher der einzig zugelassene Vertreter für diese Indikation unter den vorgestellten Biologika ist.

Schlussfolgerungen Die Biologika haben die Behandlung der Uveitis revolutioniert und sind aus der aktuellen Therapie der intraokularen Entzündung nicht mehr wegzudenken. Biologika werden bei Ineffektivität oder Unverträglichkeit konventioneller immunsuppressiver Medikamente empfohlen, aber auch bei der Therapie von schwerwiegenden Uveitisformen (z. B. Morbus Behçet). Die TNF-α-Inhibitoren sind die am häufigsten verwendeten Biologika bei Uveitis.



Publication History

Received: 26 November 2021

Accepted: 06 January 2022

Article published online:
14 April 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • 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
  • 4 Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol 2014; 6: a016295
  • 5 Babon JJ, Varghese LN, Nicola NA. Inhibition of IL-6 family cytokines by SOCS3. Semin Immunol 2014; 26: 13-19
  • 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
  • 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
  • 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
  • 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
  • 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
  • 11 Weinstein JE, Pepple KL. Cytokines in uveitis. Curr Opin Ophthalmol 2018; 29: 267-274
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 20 Jaffe GJ, Dick AD, Brezin AP. et al. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med 2016; 375: 932-943
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 33 Mushtaq B, Saeed T, Situnayake RD. et al. Adalimumab for sight-threatening uveitis in Behcetʼs disease. Eye (Lond) 2007; 21: 824-825
  • 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
  • 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
  • 36 Martel JN, Esterberg E, Nagpal A. et al. Infliximab and adalimumab for uveitis. Ocul Immunol Inflamm 2012; 20: 18-26
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 58 Miserocchi E, Giuffre C, Caporali R. et al. Secukinumab in HLA-B27 associated uveitis. Clin Exp Ophthalmol 2021; 49: 388-389
  • 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
  • 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
  • 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
  • 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
  • 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
  • 64 Deuter C, Stubiger N, Zierhut M. Interferon-alpha therapy in noninfectious uveitis. Dev Ophthalmol 2012; 51: 90-97
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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