Subscribe to RSS
DOI: 10.1055/s-0028-1086031
© Georg Thieme Verlag KG Stuttgart · New York
TNFα-blocking Agents or Conventional Immunosuppressive Drugs in the Therapy of Children with Uveitis? – An Evidence Based Approach
TNFα-blockierende Substanzen oder konventionelle Immunsuppressiva für die Behandlung von Kindern mit Uveitis? – Eine evidenzbasierte AnalysePublication History
Publication Date:
23 October 2008 (online)
![](https://www.thieme-connect.de/media/klinpaed/200806/lookinside/thumbnails/10.1055-s-0028-1086031-1.jpg)
Abstract
Treatment of childhood uveitis associated with juvenile idiopathic arthritis (JIA) is a challenge for both, ophthalmologists and pediatricians. In this study, we use the tools of evidence based medicine (EBM) to analyse studies concerning disease-modifying antirheumatic drugs (DMARD)/ immunosuppressive drugs and tumor necrosis factor alpha (TNFα) blocking agents. Most experience among DMARD's/ immunosuppressive drugs has been obtained with methotrexate (MTX) in juvenile idiopathic arthritis. However, controlled studies in uveitis are still missing, so that treatment with MTX and all other immunosuppressive drugs (ciclosporine A, azathioprine, mycophenolate mofetil) only reaches an evidence level III (expert opinion, clinical experience or descriptive study). Studies on TNFα-blocking agents reach an evidence level II–III, depending on the substance. In future, MTX will have to be examined in comparison to the new biological substance classes (e.g., tumor necrosis factor-α-blockers) for the treatment of uveitis in juvenile idiopathic arthritis. Controlled studies which have led to the approval of drugs for JIA are needed for uveitis in order to have the most effective and safe therapy for children with uveitis, who do not respond to conventional therapy with local and systemic steroids.
Zusammenfassung
Die Behandlung der JIA-assoziierten Uveitis im Kindes-und Jugendalter (JIA - Juvenile Idiopathische Arthritis) stellt eine Herausforderung sowohl für Augenärzte als auch für Kinderärzte dar. Anhand der Methoden der evidenzbasierten Medizin (EBM) haben wir in dieser Analyse Studien über DMARDs, Immunsuppressiva und Tumor-Nekrose-Faktor-α-blockierenden Substanzen untersucht. Bei der Behandlung der JIA besteht die meiste Erfahrung unter den DMARDs und Immunsuppressiva mit dem Medikament Methotrexat (MTX). Bei der Behandlung der Uveitis fehlen kontrollierte Studien, so dass der Evidenzgrad für die Behandlung mit Methotrexat und anderen Immunsuppressiva (CSA, Azathioprin und MMF) nur den Evidenzgrad III (Expertenmeinung) erreicht. Die Studien bei der Uveitis über TNF-blockierende Substanzen erreichen einen Evidenzgrad II – III, abhängig von der Substanz. In Zukunft wird zur Beurteilung der Effektivität unbedingt notwendig sein, MTX gegen die neuen Biologica zu testen. Kontrollierte Studien, die bei der JIA zur Zulassung der Medikamente geführt haben, sind auch für die Uveitis zu fordern, damit Kindern und Jugendlichen mit einer Uveitis eine effektive und sichere Therapie angeboten werden kann, wenn die konventionelle Therapie und lokal wie systemisch applizierte Steroide versagen.
Key words
uveitis - juvenile idiopathic arthritis - immunosuppression - methotrexate - TNFα-blocking agents - etanercept - infliximab - adalimumab - evidence based medicine
Schlüsselwörter
Uveitis - juvenile idiopathische Arthritis - Immunsuppression - Methotrexat - TNFα-Inhibitoren - Etanercept - Infliximab - Adalimumab - evidence based medicine
References
- 1 Becker MD, Smith JR, Max R. et al . Management of sight-threating uveitis: new therapeutic options. Drugs. 2005; 65 497-519
- 2 Beritez-Del-Castillo JM, Carcia-Sanchez J, Iradier T. et al . Sulfasalzine in the prevention of anterior uveitis associated with ankylosing spondylitis. Eye. 2000; 14 ((Pt3A)) 340-343
- 3 Biester S, Deuter C, Michels H. et al . Adalimumab in the therapy of uveitis in childhood. Br J Ophthalmol. 2007; 91 319-324
- 4 Boer J de, Wulffraat N, Rothova A. Visual loss in uveitis in childhood. Br J Ophthalmol. 2003; 87 879-884
- 5 Doycheva DG, Deuter C, Stuebiger N. et al . Mycophenolate mofetil in the treatment of uveitis in children. Br J Ophthalmol. 2007; 91 180-184
- 6 Edelsten C, Reddy MA, Stanford MR. et al . Visual loss associated with pediatric uveitis in english primary and referral centers. Am J Ophthalmol. 2003; 135 676-680
-
7 Feldmann W.
Evidence-based Pediatrics . 1 ed. Hamilton: B. Decker 2000 - 8 Foeldvari I, Wierk A. Methotrexate is an effective treatment for chronic uveitis associated with juvenile idiopathic arthritis. J Rheumatol. 2005; 32 362-365
- 9 Foeldvari I, Nielsen S, Kümmerle-Deschner J. Tumor necrosis factor-alpha blocker in the treatment of juvenile idiopathic arthritis-associated uveitis refractory to second-line agents: results of a multinational survey. J Rheumatol. 2007; 634 1146-1150
- 10 Galor A, Jabs DA, Leder HA. et al . Comparison of antimetabolite drugs as corticosteroid-sparing therapy for noninfectious ocular inflammation. Ophthalmol. 2008; , Epub ahead of print
- 11 Gerloni V, Cimaz R, Gattinara M. et al . Efficacy and safety profile of Cyclosprine A in the treatment of juvenile chronic (idiopathic) arthritis. Results of a 10-year prospective study. Rheumatology. 2001; 40 907-913
- 12 Giannini EH, Brewer EJ, Kuzmina N. et al . Result of the USA – UDSSR double-blind, placebo-controlled trial. N Engl J Med. 1992; 326 1043-1049
- 13 Guignard S, Gossec L, Salliot C. et al . Efficacy of tumor necrosis factor blockers in reducing uveitis flares in patients with spondylarthropathy: a retrospctive study. Ann Rheum Dis. 2006; 65 1631-1634
- 14 Heiligenhaus A, Mingels A, Heinz C. et al . Methotrexate for uveitis associated with juvenile idiopathic arthritis: value and requirement for additional anti inflammatory medication. Eur J Ophthalmol. 2007; 17 743-748
- 15 Heiligenhaus A, Horneff G, Greiner K. et al . Inhibitors of tumor necrois factor alpha for the treatment of arthritis and uveitis in childhood. Klin Monatsbl Augenheilkd. 2007; 224 526-531
- 16 Hemady RK, Baer JC, Foster CS. Immunosuppressive drugs in the management of progressive, corticosteroid-resistant uveitis associated with juvenile rheumatoid arthritis. Int Ophthalmol Clin. 1992; 32 241-252
- 17 Kaiplainen-Seppänen O, Leino M. Recurrent uveitis in a patient with juvenile spondylarthropathy associated with tumor necrosis factor inhibitors. Ann Rheum Dis. 2003; 62 88-89
- 18 Kilmartin DJ, Forrester JV, Dick AD. Cyclosporine A therapy in refracotry noninfectious childhood uveitis. Br J Ophthalmol. 1998; 82 737-742
- 19 Kotaniemi K. Late onset uveitis in juvenile-type chronic polyarthritis controlled with prednisolone, cyclosporine A and methotrexate. Clin Exp Rheumatol. 1998; 16 549-571
- 20 Kvien TK, Hoyerall HM, Sandstad B. Azathioprine versus placebo in patients with juvenile rheumatoid arthritis: a single center double blind comparative study. J Rheumatol. 1986; 13 118-123
- 21 Lau CH, Comer M, Lightman S. Long-term efficacy of mycophonolate mofetil in the control of severe intaocular inflammation. Clin Experiment Ophthalmol. 2003; 31 487-491
- 22 Lazar M, Weiner MJ, Leopold IH. Treatment of uveitis with methotrexate. Am J Ophthalmol. 1969; 67 383-387
- 23 Lovell DJ, Giannini EH, Reiff A. et al . Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheujmatoid arthritis: interim results from an ongoing multicenter, open-labe, extended-treatment trial. Arthritis Rheum. 2003; 48 218-226
- 24 Lovell DJ, Reiff A, Jones OY. et al . Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2006; 54 1987-1994
- 25 Lovell DJ, Reiff A, Ilowite NT. et al . Safety and efficacy of up to eight years of continuous etanercept therapy in patients with juvenile rheumatoid arthritis. Arthritis Rheum. 2008; 58 1496-1504
- 26 Munoz-Fernandez S, Hidalgo V, Fernandez-Melon J. et al . Sulfasalzine reduces the number of flares of acute anterior uveitis over a one-year period. J Rheumatol. 2003; 30 1277-1279
- 27 Rajaraman RT, Kumura Y, Li S. et al . Retrospective case review of pediatric patients with uveitis treated with infliximab. Ophthalmology. 2006; 113 308-314
- 28 Reddy AR, Backhouse OC. Does etanercept induce uveitis?. Br J Ophthalmol. 2005; 89 925
- 29 Reiff A, Takei S, Sadeghi S. et al . Etanercept therapy in children with treatment-resistant uveitis. Arthritis Rheum. 2001; 44 1411-1415
- 30 Richards JC, Tay-Kearney ML, Murray K. et al . Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Exp Ophthalmol. 2005; 33 461-468
- 31 Ruperto N, Murray KJ, Gerloni V. et al . A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate. Arthritis Rheum. 2004; 50 2191-2201
- 32 Ruperto N, Lovell DJ, Cuttica R. et al . A randomized, placebo-controlled trial of infliximab plus methotrexate for the treatment of polyarticular-course juvenile rheumatoid arthritis. Arthritis Rheum. 2007; 56 3096-3106
- 33 Sackett DL, Rosenberg WM, Gray JA. Evidence based medicine: what it is and what it isn’t. BMJ. 1996; 13 71-72
- 34 Samson CM, Waheed N, Baltatzis S. et al . Methotrexate therapy for chronic noninfectious uveits: analyses of a case series of 160 patients. Ophthalmolgy. 2001; 108 1134-1139
- 35 Saurenmann RK, Levin AV, Rose JB. et al . Tumor necrosis factor alpha inhibitors in the treatment of childhood uveitis. Rheumatology. 2006; 45 982-989
- 36 Schlote T, Danecker G, Thiel HF. et al . Cyclosporine A in therapy of chronic uveitis in childhood. Ophthalmologe. 1996; 93 745-748
- 37 Schmeling H, Horneff G. Etanercept and uveitis in patients with juvenile idiopathic arthritis. Rheumatology. 2005; 44 1008-1011
- 38 Shetty AK, Zganjar BE, Ellis Jr GS. et al . Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis. J Pediatr Ophthalmol Strabismus. 1999; 36 125-129
- 39 Smith JR, Levinson RD, Holland GN. et al . Differential efficacy of tumor necrosis factor inhibition in the management of inflammatory eye disease and associated rheumatic diesease. Arthritis Rheum. 2001; 45 252-257
- 40 Smith JA, Thompson DJ, Whitcup SM. et al . A randomized, placebo controlled, double-masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis. Arthritis Rheum. 2005; 53 18-23
- 41 SUN-Working Study Group . Perspectives-standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. J Ophthalmol. 2005; 140 509-516
- 42 Tappeiner C, Roesel M, Heinz C. et al . Limited value of cyclosporine A for the treatment of patients with uveitis associated with juvenile idiopathic arthritis. Eye. 2008; , Epub ahead of print
- 43 Tynjälä P, Lindahl P, Honkanen V. et al . Infliximab and etanercept in the treatment of chronic uveitis associated with refractory juvenile idiopathic arthritis. Ann Rheum Dis. 2007; 66 548-550
- 44 Rossum MA van, Fiselier TJ, Franssen MJ. Dutch Juvenile Chronic Arthritis Study Group . Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Arthritis Rheum. 1998; 41 808-816
- 45 Weiss AH, Wallace CA, Sherry DD. Methotrexate for resistant chronic uveitis in children with juvenile rheumatoid arthritis. J Pediatr. 1998; 133 266-268
- 46 Wells G, Haguenauer D, Shea B. et al . Cyclosporine for rheumatoid arthritis. Cochrane Database Syst Rev. 2006; 2 CD001083
- 47 Woo P, Southwood TR, Prieur AM. et al . Randomized, placebo-controlled, crossover trial of low-dose oral methotrexate in children with extended oligoarticular or systemic arthritis. Arthritis Rheum. 2000; j43 1849-1857
Correspondence
Dr. Sibylle Winterhalter
Department of Ophthalmology
University Hospital Düsseldorf Moorenstr. 5
40225 Düsseldorf
Germany
Phone: +49/211/81 173 22
Fax: +49/211/81 195 57
Email: billewin@gmx.de