Anti-TNF-  therapy for sight threatening uveitis

Lindstedt, Eric W; Baarsma, G.S.; Kuijpers, Robert W A M; Hagen, P. Martin van

doi:10.1136/bjo.2003.037192

Cited by 158 publications

(78 citation statements)

References 22 publications

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“…1,[7][8][9][10]21,23,24 In rat eye with EIU, the p75 TNF-a soluble receptor-IgG1 fusion protein (etanercept) significantly reduced the uveitis scores and cell infiltration in ocular tissues when administered 24 h before disease . 23 In a rabbit model of EIU, infliximab at a dose of 20 mg kg À1 was given intravenously 24 h before the lipopolysaccharide (LPS) challenge, resulting in a significant reduction in the clinical scores of uveitis, together with a reduced number of cell infiltration and protein exudation.…”

Section: Discussionmentioning

confidence: 99%

“…7,15 Infliximab was found beneficial also in small series of patients with intraocular inflammation associated with various ailments. 7,8 However, to date, no controlled, randomized study has identified the optimal regimen and the clear indications of anti-TNF treatments in the management of intraocular inflammation. Also, no study is available to support the use of one specific compound in these indications, even if infliximab appears more efficient than etanercept, and associated to reduced numbers of induced uveitis.…”

Section: Discussionmentioning

confidence: 99%

“…8,26 Studies derived mostly from investigator-sponsored trials and uncontrolled case series of patients have suggested that TNF antagonists, mainly infliximab, are useful in the treatment of ocular inflammation associated with Behçet's disease, rheumatoid arthritis, juvenile arthritis, ankylosing spondyloarthritis, Crohn's disease and sarcoidosis. 7,15 Infliximab was found beneficial also in small series of patients with intraocular inflammation associated with various ailments.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Based on these initial findings, pilot studies have demonstrated the efficacy of anti-TNFa strategies for the treatment of refractory uveitis using either etanercept (a p75 TNF receptor fusion protein), infliximab (a chimeric immunoglobulin G (IgG) monoclonal antibody (mAb) directed against TNF-a) or adalimumab (a human monoclonal TNF-a antibody). 7,8 In these patients systemic administration of antibodies directed toward TNF-a (infliximab or adalimumab) appeared more beneficial than the administration of the p75 TNF soluble receptor fusion protein (etanercept). 9,10 In EAU, neutralizing TNF-a activity with a systemic p55 TNF receptor fusion protein (TNFR-Ig) delayed the onset of inflammation and suppressed Th1 effector mechanisms protecting against retinal damage in the treated rats.…”

Section: Introductionmentioning

confidence: 99%

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Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

et al. 2009

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Intraocular inflammation has been recognized as a major factor leading to blindness. Because tumor necrosis factor-a (TNF-a) enhances intraocular cytotoxic events, systemic anti-TNF therapies have been introduced in the treatment of severe intraocular inflammation, but frequent re-injections are needed and are associated with severe side effects. We have devised a local intraocular nonviral gene therapy to deliver effective and sustained anti-TNF therapy in inflamed eyes. In this study, we show that transfection of the ciliary muscle by plasmids encoding for three different variants of the p55 TNF-a soluble receptor, using electrotransfer, resulted in sustained intraocular secretion of the encoded proteins, without any detection in the serum. In the eye, even the shorter monomeric variant resulted in efficient neutralization of TNF-a in a rat experimental model of endotoxininduced uveitis, as long as 3 months after transfection. A subsequent downregulation of interleukin (IL)-6 and iNOS and upregulation of IL-10 expression was observed together with a decreased rolling of inflammatory cells in anterior segment vessels and reduced infiltration within the ocular tissues. Our results indicate that using a nonviral gene therapy strategy, the local self-production of monomeric TNF-a soluble receptors induces a local immunomodulation enabling the control of intraocular inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

et al. 2009

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“…Результаты небольших иссле-дований и отдельные наблюдения свидетельствуют о том, что у некоторых пациентов с рефрактерным уве-итом лечение ингибиторами ФНО α эффективно [21]. Например, лечение препаратами этой группы прово-дили у 13 пациентов с тяжелым увеитом, у которых от-мечалось ухудшение состояния, несмотря на приме-нение других иммуносупрессивных средств, или раз-вивались серьезные побочные реакции [22]. У 6 паци-…”

Section: эффективность антагонистов фно α α в лечении увеитаunclassified

UVEITIS INA RHEUMATOLOGISTS PRACTICE: A ROLE OF TUMOR NECROSIS FACTOR-а INHIBITORS

Моисеев¹

2009

Modern Rheumatology Journal

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Uveitis frequently develops in patients with ankylosing spondylitis (AS) and other autoimmune diseases. It is occasionally characterized by a severe recurrent course and untreatable with systemic glucocorticoids (GC) and standard immunosuppressive agents. The results of (mainly small) clinical trials, as well as some observations suggest that therapy with tumor necrosis factor-α (TNF-α) inhibitors is effective in such

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Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti–tumor necrosis factor agents infliximab and etanercept

Braun¹,

Baraliakos²,

Listing³

et al. 2005

Arthritis & Rheumatism

380

176

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Objective. To estimate the incidence of anterior uveitis in patients with ankylosing spondylitis (AS) who underwent anti-tumor necrosis factor (anti-TNF) therapy, using data from recently performed trials.Methods. Data from 4 placebo-controlled studies with anti-TNF agents in AS (2 with etanercept and 2 with infliximab) and 3 open-label studies were analyzed for the prestudy prevalence and the incidence of reported flares of anterior uveitis.Results. A total of 717 patients who received treatment for anterior uveitis during the course of published clinical studies were identified by a systematic literature search using Medline. Followup information on the course of anterior uveitis was available for 397 patients. Of these, 297 were exposed to etanercept and 90 were exposed to infliximab for a total of 430 and 146.4 years, respectively. Among 190 patients who received placebo, the overall exposure was 70.5 years. The frequency of flares of anterior uveitis in the placebo group was 15.6 per 100 patient-years (95% confidence interval 7.8-27.9), while the patients treated with anti-TNF agents had a mean of only 6.8 anterior uveitis flares per 100 patient-years (P ‫؍‬ 0.01). Flares of anterior uveitis occurred less frequently (although not significantly) in patients treated with infliximab than in patients treated with etanercept (3.4 per 100 patientyears and 7.9 per 100 patient-years, respectively).Conclusion. Treatment of AS patients with biologic agents directed against TNF␣ is associated with a significant decrease in the number of anterior uveitis flares. This reduction was slightly more marked among patients treated with infliximab, but the difference was not significant.Ankylosing spondylitis (AS) is a frequently occurring chronic inflammatory rheumatic disease that causes inflammation at diverse sites, such as the spine, peripheral joints, and entheses. The most frequently occurring extraspinal involvement is inflammation of the uvea. In fact, the prevalences reported for anterior uveitis in patients with AS range from 30% to 40% (1). Tumor necrosis factor ␣ (TNF␣) is believed to play a major role in the pathogenesis of AS and other spondylarthritides. Treatment strategies involving anti-TNF agents have recently proven rather successful (2-4). Both infliximab and etanercept have been approved for the treatment of patients with active AS, both in Europe and in the US. Based on data from trials of infliximab and etanercept, it became clear that the main symptoms of AS, i.e., inflammatory back pain, peripheral arthritis, and enthesitis, are highly responsive to this therapy. However, the data for anterior uveitis are less clear.The aim of this study was to analyze the cumulative recent experience in terms of the incidence of anterior uveitis among patients with AS who were treated with anti-TNF agents and placebo. PATIENTS AND METHODSAlthough the total number of published reports of controlled trials with anti-TNF␣ agents is already quite substantial, the number of reports that describe the history of anterior u...

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Anti-TNF- therapy for sight threatening uveitis

Cited by 158 publications

References 22 publications

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

Effects of ciliary muscle plasmid electrotransfer of TNF-α soluble receptor variants in experimental uveitis

UVEITIS INA RHEUMATOLOGISTS PRACTICE: A ROLE OF TUMOR NECROSIS FACTOR-а INHIBITORS

Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti–tumor necrosis factor agents infliximab and etanercept

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