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.