Comparative Real-World Effectiveness of Immunomodulatory Therapies for Prevention of Uveitis Relapse in Behçet Disease.

Abstract

To evaluate comparative effectiveness of cyclosporine, interferon alfa-2a, and adalimumab for the prevention of uveitis relapse in Behçet disease in real-world settings. We emulated a target trial involving adult patients with Behçet disease uveitis who initiated cyclosporine, interferon alfa-2a, or adalimumab between April 10, 2008, and August 1, 2024, and were observed up until September 10, 2024. We applied overlap weighting to balance patient characteristics across treatment groups and emulate randomization at baseline. The primary outcome was the annualized relapse rate of uveitis during treatment with study therapy. The cohort comprised 716 cyclosporine users, 193 interferon alfa-2a users, and 103 adalimumab users. The estimated mean annualized relapse rate of uveitis was 0.95 (95% confidence interval [CI] 0.82-1.10) with cyclosporine, 0.52 (95% CI 0.40-0.69) with interferon alfa-2a, and 0.28 (95% CI 0.19-0.43) with adalimumab. Patients treated with cyclosporine experienced more relapses than those treated with adalimumab (incidence rate ratio [IRR] 3.36 [95% CI 2.23-5.05]; mean difference 0.66 [95% CI 0.48-0.85]; P < 0.001) or interferon alfa-2a (IRR 1.81 [95% CI 1.37-2.4]; mean difference 0.42 [95% CI 0.22-0.62]; P < 0.001). The relapse rate was higher with interferon alfa-2a than with adalimumab (IRR 1.86 [95% CI 1.16-2.97]; mean difference 0.24 [95% CI 0.05-0.43]; P = 0.011). In Behçet disease, interferon alfa-2a was associated with a reduction in uveitis relapse compared with cyclosporine, whereas adalimumab demonstrated a stronger association with reduced relapse than interferon alfa-2a.