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to change to another TNF-α blocker, even when the second drug
may previously have become ineffective too? Manfred Zierhut is an Associate Professor of
Ophthalmology at the University Eye Hospital in
Tübingen. His scientific interests include clinical and
We have to be aware that nowadays the development of drugs,
experimental immunology, especially in uveitis,
especially biologicals, is so rapid that some of these important conjunctivitis and keratitis, eye diseases caused by
questions may not be answered before the ‘new drug’ has become an
systemic disorders, immunological mechanisms
leading to uveitis, therapy of Behçet’s disease,
‘old drug’ and been substituted by a more recent agent. However,
allergies of the eye and dry-eye syndromes. Dr Zierhut
these open questions should lead to extremely careful use of TNF-α is a member of the Intermedial Uveitis Study Group,
blockers in all patients with uveitis, but especially in children. All of
the Inflammation Society and the Tear Film and Ocular Surface Society (TFOS). He
has 105 original publications in journals, 62 chapters in books and 190 posters/
the published data demonstrate very good effects in children in
proceedings of meetings and abstracts, is the editor of 24 books, has given more
whom the previous therapy was not effective, showing that these than 600 lectures and has been the chief organiser of 32 workshops or meetings.
drugs can help even in situations that seem to be hopeless. The first
Dr Zierhut is Editor in Chief of Ocular Immunology and Inflammation. He also heads
the German and European Uveitis Patient Interest Groups. He completed his
five- or even 10-year observations will hopefully tell us that TNF-α-
residency at the Universities of Hannover and Tübingen and a fellowship at
blocking drugs have enormously changed the prognosis of paediatric Massachusetts Eye and Ear Infirmary at Harvard Medical School.
uveitis, a previously often blinding disease. n
1. Zierhut M, Doycheva D, Biester S, et al., Therapy of uveitis 11. Kaipiainen-Seppänen O, Leino M, Recurrent uveitis in a 21. Richards JC, Tay-Kearney ML, Murray K, et al., Infliximab for
in children, Int Ophthalmol Clin, 2008;48(3):131–52. patient with juvenile spondyloarthropathy associated with juvenile idiopathic arthritis-associated uveitis, Clin
2. de Vos AF, van Haren MAC, Verhagen C, et al., TNF-induced tumour necrosis factor alpha inhibitors, Ann Rheum Dis, Experiment Ophthalmol, 2005;33:461–8.
uveitis in the Lewis rat is associated with intraocular 2003;62:88–9. 22. Sharma SM, Ramanan AV, Riley P, et al., Use of infliximab
interleukin 6 production, Exp Eye Res, 1995;60:199–207. 12. Lim LL, Fraunfelder FW, Rosenbaum JT, Do tumor necrosis in juvenile onset rheumatological disease-associated
3. Rosenbaum JT, Howes EL, Rubin RM, et al., Ocular factor inhibitors cause uveitis? A registry-based study, refractory uveitis: efficacy in joint and ocular disease,
inflammatory effects of intravitreally-injected tumor Arthritis Rheum, 2007;56:3248–52. Ann Rheum Dis, 2007;66:840–41.
necrosis factor, Am J Pathol, 1988;133:47–53. 13. Guignard S, Gossec L, Salliot C, et al., Efficacy of tumour 23. Foeldvari I, Nielsen S, Kümmerle-Deschner J, et al., Tumor
4. Lacomba MS, Martin CM, Galera JMG, et al., Aqueous necrosis factor blockers in reducing uveitis flares in necrosis factor-alpha blocker in treatment of juvenile
humor and serum tumor necrosis factor-α in clinical patients with spondyloarthropathy: a retrospective study, idiopathic arthritis-associated uveitis refractory to second-
uveitis, Ophthalmic Res, 2001;33:251–5. Ann Rheum Dis, 2006;65:1631–4. line agents: results of a multinational survey, J Rheumatol,
5. Brito BE, O’Rourke LM, Pan Y, et al., IL-1 and TNF receptor- 14. Stübgen JP, Tumor necrosis factor-alpha antagonists and 2007;34:1146–50.
deficient mice show decreased inflammation in an neuropathy, Muscle Nerve, 2007;37:281–92. 24. Tynjälä P, Lindahl P, Honkanen V, et al., Infliximab and
immune complex model of uveitis, Invest Ophthalmol, 15. Simsek I, Erdem H, Pay S, et al., Optic neuritis occurring etanercept in the treatment of chronic uveitis associated
1999;40:2583–9. with anti-tumour necrosis factor α therapy, Ann Rheum Dis, with refractory juvenile idiopathic arthritis, Ann Rheum Dis,
6. Dick AD, McMenamin PG, Körner H, et al., Inhibition of 2007;66:1255–8. 2007;66:548–50.
tumor necrosis factor activity minimizes target organ 16. Smith JA, Thompson DJ, Whitcup SM, et al., A randomized, 25. Galor A, Perez VL, Hammel JP, et al., Differential
damage in experimental autoimmune uveoretinitis despite placebo-controlled, double-masked clinical trial of effectiveness of etanercept and infliximab in the treatment
quantitatively normal activated T cell traffic to the retina, etanercept for the treatment of uveitis associated with of ocular inflammation, Ophthalmology, 2006;113:2317–23.
Eur J Immunol, 1996;26:1018–25. juvenile idiopathic arthritis, Arthritis Rheum, 2005;53:18–23. 26. Biester S, Deuter C, Michels H, et al., Adalimumab in the
7. Wolbink GJ, Vis M, Lems W, et al., Development of 17. Biester S, Michels H, Haefner R, et al., Etanercept in the therapy of uveitis in childhood, Br J Ophthalmol, 2007;91:
antiinfliximab antibodies and relationship to clinical treatment of chronic anterior uveitis in children, Invest 319–24.
response in patients with rheumatoid arthritis, Arthritis Ophthalmol Vis Sci Abstract ARVO, 2004;2668. 27. Vazquez-Cobian LB, Flynn T, Lehman TJ, Adalimumab
Rheum, 2006;54:711–15. 18. Foster CS, Tufail F, Waheed NK, et al., Efficacy of etanercept therapy for childhood uveitis, J Pediatr, 2006;149:572–5.
8. Soykan I, Ertan C, Ozden A, Severe anaphylactic reaction in preventing relapse of uveitis controlled by methotrexate, 28. Tynjälä P, Kotaniemi K, Lindahl P, et al., Adalimumab in
to infliximab: report of a case, Am J Gastroenterol, 2000;95: Arch Ophthalmol, 2003;121:437–40. juvenile idiopathic arthritis-associated chronic anterior
2395–6. 19. Saurenmann RK, Levin AV, Rose JB, et al., Comparison of uveitis, Rheumatology (Oxford), 2008;47:339–44.
9. Fonollosa A, Segura A, Giralt J, et al., Tuberculous uveitis infliximab with etanercept in pediatric uveitis, Graefes Arc 29. Jabs DA, Nussenblatt RB, Rosenbaum JT, Standardization of
after treatment with etanercept, Graefes Arch Clin Exp Clin Exp Ophthalmol, 2006;244:281–90. uveitis nomenclature (SUN) Working Group. Standardization
Ophthalmol, 2007;245:1397–9. 20. Rajaraman RT, Kimura Y, Li S, et al., Retrospective case of uveitis nomenclature for reporting clinical data. Results
10. Reddy AR, Backhouse OC, Does etanercept induce review of pediatric patients with uveitis treated with of the First International Workshop, Am J Ophthalmol,
uveitis?, Br J Ophthalmol, 2003;87:925. infliximab, Ophthalmology, 2006;113:308–14. 2005;140:509–16.
Adalimumab in Juvenile Idiopathic Arthritis-associated Chronic Anterior Uveitis
Tynjälä P, et al., Rheumatology (Oxford), 2008;47:339–44.
The aim of this study was to evaluate the efficacy of adalimumab in therapy was 18.7 months. Of the 20 patients, seven (35%) showed
juvenile idiopathic arthritis (JIA)-associated uveitis. This entailed a improved activity, one (5%) showed worsening activity and in 12 (60%)
retrospective observational study of 20 patients with JIA and chronic no change was observed in the activity of uveitis. Those with improved
uveitis on adalimumab treatment. The ocular inflammation and activity were younger and had shorter disease duration. The mean
improvement was assessed according to the Standardization of Uveitis number of flares/year decreased from 1.9 to 1.4. Serious adverse
Nomenclature (SUN) criteria. Results showed at the initiation of events or side effects were not observed. Seven patients discontinued
adalimumab the mean age of patients was 13.4 years and the mean adalimumab during the follow-up: six because of inefficacy and one
duration of uveitis was 8.7 years. Seventeen patients (85%) had because of inactive uveitis. The study concluded that adalimumab is a
polyarticular JIA and 19 (95%) had previously been on anti-tumour potential treatment option in JIA-associated uveitis, even in patients
necrosis factor (TNF) treatment. The mean duration of adalimumab non-responsive to previous other anti-TNF therapy. n
88 EUROPEAN OPHTHALMIC REVIEW