Adalimumab vs. Conventional Immunosuppression for Uveitis (ADVISE) Trial.

Objective: Patients with non-infectious intermediate, posterior, or panuveitides typically are treated with oral corticosteroids and immunosuppressive agents, such as antimetabolites and calcineurin inhibitors. Goals of treatment include suppression of ocular inflammation (inactive disease) and reduction of oral corticosteroids to a prednisone dose <7.5 mg/day (corticosteroid sparing) or, if possible, discontinuation of prednisone. The anti-tumor necrosis factor monoclonal antibody, adalimumab, also is used in the treatment of these diseases, but its comparative effectiveness to conventional agents is unknown. The purpose of this trial was to compare adalimumab treatment to that with conventional immunosuppressive drugs for uveitis.

Design: Randomized, unmasked, comparative effectiveness trial conducted at uveitis clinics at academic medical centers and private practices in the United States and internationally PARTICIPANTS: Patients with active or recently active non-infectious intermediate, posterior, or panuveitides needing immunosuppression INTERVENTIONS: Adalimumab vs. conventional immunosuppressive drugs (antimetabolites and/or calcineurin inhibitors) MAIN OUTCOME MEASURES: The primary outcome was successful corticosteroid sparing, defined as inactive uveitis at a prednisone dose <7.5 mg/day (or its equivalent) for 2 consecutive study visits >28 days apart, at 6 months. Other outcomes included successful corticosteroid sparing at 1 year and successful corticosteroid discontinuation, defined as inactive uveitis and no oral corticosteroid therapy for 2 consecutive study visits >28 days apart RESULTS: 227 participants were randomized to either adalimumab (N=114) or conventional immunosuppression (N=113). By 6 months of follow-up successful corticosteroid sparing occurred in 69% of participants assigned to adalimumab vs. 54% assigned to conventional immunosuppression (odds ratio [OR] 1.86; 95% confidence interval [CI] 1.06, 3.25; P=0.029) and by 12 months in 86% of participants assigned to adalimumab vs. 77% assigned to conventional immunosuppression (OR 1.89; 95% CI 0.93, 3.83; P=0.077). By 12 months successful corticosteroid discontinuation occurred in 55% of participants assigned to adalimumab vs. 40% assigned to conventional immunosuppression (OR 1.85; 95% CI 1.06, 3.19: P=0.028).

Conclusions: For patients with non-infectious intermediate, posterior, or panuveitides requiring immunosuppression, adalimumab treatment resulted in a greater proportion of participants with successful corticosteroid sparing at 6 months and successful corticosteroid discontinuation at 12 months compared to treatment with antimetabolites or calcineurin inhibitors.