Immunosuppression for the Uveitides

Abstract

The uveitides are a collection of more than 30 diseases characterized by intraocular inflammation. Many cases of juvenile idiopathic arthritis-associated uveitis, many cases of intermediate uveitis, and most cases of posterior and panuveitides requiring treatment are treated with corticosteroids and immunosuppression. Disease-specific, time-updated modeling of clinical data for several uveitides suggests superior prevention of ocular complications and visual outcomes with immunosuppression. These studies also suggest that oral corticosteroids at doses low enough for safe long-term therapy (i.e., <7.5 mg/day) are ineffective, implying that immunosuppression should be part of the initial regimen. The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study was a randomized comparative effectiveness trial comparing systemic therapy with oral corticosteroids and immunosuppression with regional corticosteroid treatment. It demonstrated that, when used properly, oral corticosteroids and immunosuppression can be given safely for up to 7 years with no evident increased risk of systemic side effects compared with regional corticosteroid therapy, except for greater antibiotic use for infections. The Systemic Treatment for Eye Diseases (SITE) Cohort Study suggested long-term safety for this approach, when the immunosuppressive agents were antimetabolites or calcineurin inhibitors. Thus, oral corticosteroids and immunosuppression may be a preferred initial therapy for many noninfectious, intermediate, posterior, and panuveitides. Nonalkylating-agent immunosuppression has a low rate of sustained, drug-free remissions, <10%/year. Nonalkylating-agent immunosuppression for >3 years with control of the inflammation for >2 years is associated with a decreased risk of relapse after discontinuing immunosuppression. Alkylating agents can induce sustained drug-free remissions but likely increase the lifetime risk of cancer. Biologics, which target specific cytokines and pathways, hold promise for the future. Monoclonal antibodies directed against tumor necrosis factor (TNF)-α have been studied most often, and one, adalimumab, is U.S. Food and Drug Administration approved for the treatment of noninfectious, intermediate, posterior, and panuveitides.

The use of biologic agents in the management of uveitis

“…Patients on systemic corticosteroids (at doses >20 mg/day for >2 weeks), conventional immunomodulator drugs or biological agents are considered immunocompromised . Chronic comorbidities, including diabetes mellitus, kidney disease and pulmonary disease, also increase patient susceptibility to infections while on biologic therapies.…”

“…Patients on systemic corticosteroids (at doses >20 mg/day for >2 weeks), conventional immunomodulator drugs or biological agents are considered immunocompromised. 106 Chronic comorbidities, including diabetes mellitus, kidney disease and pulmonary disease, also increase patient susceptibility to infections while on biologic therapies. Risk management includes discussion of adherence to therapy, screening for serious latent infections, counselling regarding pathogen avoidance, early recognition of infection and prompt management of infective symptoms.…”

Inflammatory eye and rheumatic disease

“…(c) Relapse therapy (usually involving a burst of oral and/or locally administered therapy with peri‐ocular or intravitreal corticosteroids such as triamcinolone or dexamethasone to maintain remission). (d) Cessation of therapy (gradual tapering of all immunosuppression therapy) after the disease has been in sustained long‐term remission …”

Biological Therapies that Target Inflammatory Cytokines to Treat Uveitis

“…The steroid-sparing drugs have significantly improved the outcome of uveitis and provide additional more targeted treatment options [17]. However, as with steroids, these drugs may produce significant side effects, including an increased susceptibility to infection, and many still fail to provide lasting remission [2,18]. It is conceivable that a targeted therapy that only suppresses one or two inflammatory pathways may offer a more favorable side effect profile than standard steroid-sparing agents [2].…”