Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

Abstract

Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis.

Management of high-risk corneal transplantation

“…18,113,126 In a randomized, multicenter trial on 86 patients, Reinhard et al 125 showed an immune reaction free rate of 89% in the MMF-treated group compared with 67% in the control group during the first year postoperatively. After a mean follow-up of 3 years in the same cohort, Birnbaum et al 19 reported a reaction-free graft survival rate of 83% in the MMF-treated group and 64.5% in the control group.…”

Adalimumab in Active and Inactive, Non-Infectious Uveitis: Global Results from the VISUAL I and VISUAL II Trials

“…2 As uveitis often affects the young adult population in their most productive years of life, the personal and population burden of this sight-threatening disease is noteworthy. 3,4 Conventional therapy with corticosteroids (CS) has been the mainstay to treat uveitis; although CS are often effective, ocular and/or systemic adverse effects limit their long-term use. [5][6][7] Adalimumab (Humira ® ; AbbVie Inc., North Chicago, IL) is a recombinant human immunoglobulin (IgG1) monoclonal antibody that binds specifically to tumor necrosis factor (TNF) and neutralizes its biological function.…”

An Update on Treatment of Pediatric Chronic Non-infectious Uveitis

“…These agents target molecules in the immune system that play a key role in the ocular inflammatory process(54). For example, TNF alpha, interleukins (IL) and interferons are pro-inflammatory cytokines produced by immune cells and are consistently elevated in serum and aqueous fluid of patients with uveitis(55, 56).…”

“…It is FDA approved for several auto-immune conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis and inflammatory bowel disease (54). Numerous prospective and retrospective studies support IFX’s use for non-infectious uveitis, but dosage and interval vary (62–67).…”

“…In refractory uveitis, an increased dose of 20mg/kg has been used successfully (64, 68, 69). Potential side effects include, increased susceptibility to infections, reactivation of tuberculosis or histoplasmosis, malignancy and development of lupus-like syndrome (2, 54). Mild and moderate infusion reactions occurred in 17% of patients in one study (70).…”