Biotherapies in Uveitis

Abstract

Non-infectious uveitis (NIU) represents one of the leading causes of blindness in developed countries. The therapeutic strategy aims to rapidly control intra-ocular inflammation, prevent irremediable ocular damage, allow corticosteroid sparing and save the vision, and has evolved over the last few years. Anterior NIU is mostly managed with topical treatment in adults. However, for intermediate, posterior and pan-uveitis, notably when both eyes are involved, systemic treatment is usually warranted. Biotherapies are recommended in case of inefficacy or non-tolerance of conventional immunosuppressive drugs in non-anterior NIU. Anti-tumor necrosis factor alpha (anti-TNF-α) agents are by far the most widely used, especially adalimumab (ADA) and infliximab (IFX). In case of sight-threatening uveitis in Behçet’s disease or in case of risk of severe recurrences, respectively IFX and ADA may be recommended as first-line therapy. Many questions are left unanswered; how long to treat NIU, how to discontinue anti-TNF-α agents, what biologic to use in case of anti-TNF-α failure? The objective of this review is to present an updated overview of knowledge on the use of biological treatments in NIU.

Case Report: A Promising Treatment Strategy for Noninfectious Uveitis

“…When conventional immunosuppressive drugs are ineffective or have developed tolerance, biologics are the best choice for treatment, of which anti-TNF-α inhibitors are the most widely used ( Leclercq et al, 2020 ). Adalimumab has been approved by the FDA to treat patients with steroid-dependent or noninfectious uveitis with steroid contraindications ( Dick et al, 2018 ).…”

“…Infliximab is recommended as the first-line treatment for Behçet’s disease-related uveitis ( Levy-Clarke et al, 2014 ). However, the failure rate of treatment with anti-TNF-α inhibitor drugs remains high, at approximately 30% ( Leclercq et al, 2020 ). Llorenc et al analyzed 392 noninfectious uveitis patients treated with adalimumab.…”

Characterization of a Novel Caveolin Modulator That Reduces Vascular Permeability and Ocular Inflammation

“…Current treatment goals are the suppression of inflammation using steroids in combination with immunomodulators such as methotrexate, mycophenolate mofetil, and biologic modifiers in combination. 29 Key components of the inflammatory process in uveitis include the invasion of the eye by both T cells and macrophages, breakdown of the blood-retinal barrier, edema, and leakage of protein into the aqueous and vitreous. Prior work has shown that AP-Cav reduced the influx of inflammatory cells in an immune models of MS, asthma, and retinal disease [17][18][19]28 and reduced the actions and production of cytokines.…”

Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis

“…Uveitis is an intraocular inflammation of different etiologies [1][2][3][4][5] characterized by leukocyte accumulation in ocular tissues and cytokine release. It is a painful condition and is associated with redness, photophobia, impaired vision, and blindness [6][7][8][9][10] Pharmacological treatment for uveitis includes corticosteroids, chemotherapeutic agents, and tumor necrosis factor (TNF)-α inhibitors [3,7,8,11], but the use of these drugs is limited by their serious side effects, such as increased ocular pressure or cytotoxicity [9,12].…”

“…It is a painful condition and is associated with redness, photophobia, impaired vision, and blindness [6][7][8][9][10] Pharmacological treatment for uveitis includes corticosteroids, chemotherapeutic agents, and tumor necrosis factor (TNF)-α inhibitors [3,7,8,11], but the use of these drugs is limited by their serious side effects, such as increased ocular pressure or cytotoxicity [9,12]. However, recent advances in the mechanisms of inflammation and the discovery of several endogenous anti-inflammatory mediators have provided new therapeutic possibilities for uveitis treatment [5,7,10,[13][14][15].…”