Management Of Noninfectious Uveitis Research Articles

Malignancy Risk Associated With the Use of Systemic Immunomodulatory Therapy in the Management of Noninfectious Uveitis

Patients with noninfectious uveitis (NIU) can require treatment with systemic immunomodulatory therapy (IMT), but it is unclear whether IMT drug categories increase the risk of malignancy in NIU patients. The purpose of this study is to determine if the use of systemic IMT in patients with NIU is associated with an increased risk of malignancy. Clinical cohort study. Patients were identified from a US administrative medical claims database including some Medicare Advantage and commercial plans, from 2000 to 2022. About 318,498 NIU patients were identified. Enrollees were included in the analysis if they met the following criteria: continuous enrollment in the plan for at least 1 year, and at least 2 consecutive visit diagnoses of any type of NIU, after initiation of systemic IMT. We compared the rates of incident malignancy in NIU patients treated with IMT versus the rates among NIU patients not treated with IMT. Multivariable Cox regression models were used to predict the hazard of developing incident cancer. Of the 318,498 patients with NIU identified over a 15-year period, 318,006 did not develop malignancy, and 492 did develop malignancy. Of the patients that developed a malignancy, 280 (57%) were treated with systemic corticosteroids; 204 (41%) were treated with antimetabolites; 44 (9%) were treated with T cell inhibitors; 108 (22%) were treated with TNF alpha inhibitors; 2 (0.004%) were treated with interleukin-6 (IL-6) inhibitors; and 1 was treated with CD-20 antibodies. There were no malignancies reported in the group treated with alkylating agents. There was no association between any of the drug classes and incidence of malignancy. This study suggests that there is no increased risk of malignancy associated with the use of systemic IMT for patients with NIU.

Diagnosis and Management of Non-Infectious Uveitis in Pediatric Patients.

Uveitis in children accounts for 5-10% of all cases. The causes vary considerably. Classically, uveitis is distinguished according to its infectious or inflammatory origin and whether it is part of a systemic disease or represents an isolated ocular disease. It is important to highlight the specificity of certain etiologies among children such as juvenile idiopathic arthritis. The development of visual function can potentially be hindered by amblyopia (children aged <7years), in addition to the usual complications (synechiae, macular edema) seen in adult patients. Moreover, the presentation of uveitis in children is often "silent" with few warning signs and few functional complaints from young children, which frequently leads to a substantial diagnostic delay. The diagnostic approach is guided by the presentation of the uveitis, which can be characterized by its location, and corresponds to the initial and main site of intraocular inflammation; its presentation, whether acute or chronic, granulomatous or not; and the response to treatment. Pediatricians have an important role to play and must be aware of the various presentations and etiologies of uveitis in children. Juvenile idiopathic arthritis is the most common etiology of pediatric non-infectious uveitis, but other causes must be recognized. Promptly initiated treatment before complications arise requires early diagnosis, recognition, and treatment. Any dependence on prolonged local corticosteroid therapy justifies discussing the introduction of a corticosteroid-sparing treatment considering the risk to develop corticoid-induced glaucoma and cataracts. Systemic corticosteroid therapy can be required for urgent control of inflammation in the case of severe uveitis. Long-lasting immunosuppressive treatment and biotherapies are most often prescribed at the same time to reinforce treatment efficacy and to prevent relapse and corticosteroid dependency. We review the different causes of uveitis, excluding infection, and the diagnostic and therapeutic management aimed at limiting the risk of irreversible sequelae.

Subcutaneous tocilizumab in the management of non-infectious uveitis in children: a brief report

BackgroundTocilizumab is a humanized monoclonal antibody that acts as an IL-6 receptor antagonist. Intravenous tocilizumab is considered an option for children with anti-TNF refractory juvenile idiopathic arthritis-associated uveitis. In contrast, the potential of subcutaneous drug use with this indication is more controversial. Due to the decreased availability of intravenous tocilizumab during the COVID-19 pandemic, we started using the subcutaneous formulation of the drug in children with anti-TNF refractory uveitis. The study analyzes the serum concentration of tocilizumab and its clinical response in patients with anti-TNF refractory uveitis who started or switched to subcutaneous administration from intravenous use.MethodsFive patients with non-infectious uveitis were treated with subcutaneous tocilizumab. Ocular inflammation was evaluated on slit lamp examination during clinical control. Serum tocilizumab concentrations were determined by ELISA.ResultsThe mean blood concentration of tocilizumab was 61.4 µg/mL (range 2.7–137.0.), with higher values than levels recorded in adult patients with rheumatoid arthritis treated with intravenous tocilizumab. Three patients entered clinical remission. One patient developed a mild relapse and was treated with topical steroids. Only one patient did not respond to therapy. The medication was well tolerated without severe infection or other adverse events.ConclusionOur results support a possible role of subcutaneous tocilizumab in anti-TNF refractory uveitis.

Management of repository corticotropin injection therapy for non-infectious uveitis: a Delphi study.

Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission≥2years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.

Biologic Drugs for the Treatment of Noninfectious Uveitis.

The management of noninfectious uveitis is constantly evolving. A new "biologic era" in treatment began after the effectiveness of tumor necrosis factor-alpha blocking drugs was demonstrated in rheumatologic inflammatory diseases. The goal of specific immunomodulation with a biologic drug is to target inflammation at the molecular level with a low rate of serious adverse events. The purpose of this review is to summarize current knowledge of biologic drugs in the treatment of noninfectious uveitis by describing clinical studies and recent pharmacological developments.

A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis.

Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role. A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE (OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment of study aims, methods, efficacy outcomes and adverse events was performed. Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus, the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40% to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation, visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per patient-year with everolimus. Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent.

IL-6 blockade in the management of non-infectious uveitis.

Several pathogenetic studies have paved the way for a newer more rational therapeutic approach to non-infectious uveitis, and treatment of different forms of immune-driven uveitis has drastically evolved in recent years after the advent of biotechnological drugs. Tumor necrosis factor-α targeted therapies, the first-line recommended biologics in uveitis, have certainly led to remarkable results in patients with non-infectious uveitis. Nevertheless, the decision-making process turns out to be extremely difficult in anti-tumor necrosis factor or multidrug-resistant cases. Interleukin (IL)-6 holds a critical role in the pathogenic pathways of uveitis, due to its extended and protean range of effects. On this background, manipulation of IL-6 inflammatory cascade has unraveled encouraging outcomes. For instance, rising evidence has been achieved regarding the successful use of tocilizumab, the humanized monoclonal antibody targeted against the IL-6 receptor, in treating uveitis related to juvenile idiopathic arthritis or Behçet's disease. Similar findings have also been reported for uveitis associated with systemic disorders, such as rheumatoid arthritis or multicentric Castleman disease, but also for idiopathic uveitis, the rare birdshot chorioretinopathy, and even in cases complicated by macular edema. This work provides a digest of all current experiences and evidences concerning IL-6 blockade, as suggested by the medical literature, proving its potential role in the management of non-infectious uveitis.

Burden and Direct Costs of Non Infectious Uveitis in Spain

ObjectivesThere is no updated information on epidemiology and cost of management of non infectious uveitis (NIU) in Spain. This study assessed the frequency of various types of uveítis as well as associated costs of resources used in their management. Material and methodNIU epidemiological data and direct costs were collected from a literature search. This was complemented with consensus information from 2 expert panel meetings and data from questionnaires to ophthalmologists and rheumatologists, experts on these conditions. Healthcare resources costs were obtained from the Oblikue database, from a medical society and from approved drug prices in Spain. ResultsDuring 2011 the estimate number of NIU was 9398 (45% male, 70% aged 16–65 years). Incidence per type of uveitis was: acute anterior uveitis (AAU) 55%; posterior uveitis (PU) and pan-uveitis (PanU) 15% each; adult chronic anterior uveitis, pediatric chronic anterior uveitis and intermediate uveitis 5% each. Among total costs (77,834,282.10€), initial drug therapy was the highest (43,602,359.29€), followed by surgical treatment of complications (8,367,420.43€). With respect to types of uveitis, PanU (26,692,948.29€), PU (22,283,330.50€) and AAU (14,336,755.38€) showed the highest associated costs. ConclusionsNon infectious uveitis is associated to high costs in Spain, both in its diagnosis and in its treatment. Early diagnosis and treatment should allow for substantial savings for the National Health System.

Manage non-infectious uveitis in adults with individualized immunosuppressive therapy and regular monitoring

The management of non-infectious uveitis in adults is challenging and requires precise and early diagnosis to allow prompt therapeutic intervention. While topical and/or systemic corticosteroids are mainstay options, some patients require timely treatment escalation with additional agents.

Non-Infectious Uveitis: Optimising the Therapeutic Response.

Non-infectious uveitis mainly affects the working-age population and can contribute to significant social and economic burden. It comprises a heterogeneous group of conditions with varied aetiology. Precise and early diagnosis, excluding masquerade syndromes, is the key to early therapeutic intervention. Treatment should be appropriately selected according to the anatomical sites of inflammation, the diagnosis and known prognosis, and whether there is a systemic inflammatory drive. Corticosteroids in the form of local or systemic therapy form the mainstay of treatment; however, due to unacceptable side effects, the need for long-term use or suboptimal response, corticosteroid-sparing medications may need to be considered early on in the management of non-infectious uveitis. With newer insights into the immunopathology of uveitis and the availability of biologic agents, treatment can be tailored according to individual needs. Many patients have systemic involvement, and hence a multidisciplinary approach is often required to achieve the best outcome in an individual. Patient involvement in the management of non-infectious uveitis, ensuring compliance, and continual monitoring of both the treatment and therapeutic response are the key to achieving optimal outcomes.

Carga y costes directos de la uveítis no infecciosa en España

ObjectivesThere is no updated information on epidemiology and cost of management of non infectious uveitis (NIU) in Spain. This study assessed the frequency of various types of uveítis as well as associated costs of resources used in their management. Material and methodNIU epidemiological data and direct costs were collected from a literature search. This was complemented with consensus information from 2 expert panel meetings and data from questionnaires to ophthalmologists and rheumatologists, experts on these conditions. Healthcare resources costs were obtained from the Oblikue database, from a medical society and from approved drug prices in Spain. ResultsDuring 2011 the estimate number of NIU was 9,398 (45% male, 70% aged 16-65 years). Incidence per type of uveitis was: acute anterior uveitis (AAU) 55%; posterior uveitis (PU) and pan-uveitis (PanU) 15% each; adult chronic anterior uveitis, paediatric chronic anterior uveitis and intermediate uveitis 5% each. Among total costs (77,834,282.10€), initial drug therapy was the highest (43,602,359.29€), followed by surgical treatment of complications (8,367,420.43€). With respect to types of uveitis, PanU (26,692,948.29€), PU (22,283,330.50€) and AAU (14,336,755.38€) showed the highest associated costs. ConclusionsNon infectious uveitis is associated to high costs in Spain, both in its diagnosis and in its treatment. Early diagnosis and treatment should allow for substantial savings for the National Health System.

Current concepts and future directions in the pathogenesis and management of non infectious uveitis

Current concepts and future directions in the pathogenesis and management of non infectious uveitis

Voclosporin: a potentially promising therapeutic agent for noninfectious uveitis

Voclosporin is a novel calcineurin inhibitor that functions by binding cyclophilin, consequently inhibiting calcineurin activity and preventing the transcription of many genes involved in lymphocyte proliferation and cytokine release. Voclosporin has been shown to be effective in a variety of autoimmune diseases, such as rheumatoid arthritis, psoriasis and renal transplant rejection. Noninfectious uveitis is also an immune-mediated disease which, if left untreated, can cause severe loss of vision. Presently, corticosteroids are the mainstay of therapy in noninfectious uveitis. However, there are several metabolic and ophthalmic adverse effects associated with the long-term use of corticosteroids. Voclosporin has recently been shown in the LX-211 Uveitis Multicenter Investigation of a New Approach to Treatment (LUMINATE) clinical trial program to be effective in the treatment of noninfectious uveitis. With an acceptable side-effects profile, voclosporin is an exciting addition to the therapeutic options available in the management of noninfectious uveitis.