Comparative Five-Year Risks of Systemic Complications with Biologic versus Conventional Therapy in Non-infectious Uveitis.

Abstract

To compare five-year systemic complication risks in non-infectious uveitis (NIU) patients treated with systemic biologic versus conventional therapy. Multicenter retrospective clinical cohort study. Adult patients (≥18 years old) with NIU from the TriNetX Collaborative Network. We identified patients with NIU using International Classification of Diseases, Ninth and Tenth Revision, Clinical Modification codes. We assembled propensity score-matched comparisons: biologic therapy versus no systemic therapy (n=6,896 each), biologic versus conventional therapy with corticosteroids matched (n=5,994 each), between January 1, 2005, and January 1, 2024. A pre-specified subgroup analysis of Analysis 2 restricted to patients receiving combination biologic + conventional therapy versus conventional therapy alone (n=3,653 each) was also conducted. We employed time-to-event analyses to identify incidence of systemic complications. Incidence of serious infections, hematologic cytopenias, heart failure, thromboembolic events, diabetes mellitus, malignancy, psychiatric illness, all-cause hospitalization, and all-cause mortality. After propensity score matching, cohorts were balanced on all measured covariates (all standardized mean differences <0.1). Compared with no systemic therapy, biologic treatment was associated with higher five-year risks of serious infections, including pneumonia (hazard ratio [HR]: 1.41, 95% confidence interval [95% CI]: 1.20-1.67), sepsis (HR: 1.43, 95% CI: 1.16-1.77), and hematologic cytopenias (HR: 1.58, 95% CI: 1.44-1.74), representing 5-year Kaplan-Meier-estimated cumulative incidences of 6.43%, 3.87%, and 30.12%, respectively, in biologic-treated patients. Risks of heart failure, thromboembolic events, psychiatric illness, diabetes, and all-cause mortality did not significantly differ between groups. When compared with conventional immunomodulatory therapy, biologic treatment demonstrated a largely comparable five-year safety profile, with the primary exceptions of higher rates of hematologic cytopenias (HR: 1.28, 95% CI: 1.16-1.41), psychiatric illness (HR: 1.13, 95% CI: 1.01-1.27), and hospitalization (HR: 1.20, 95% CI: 1.07-1.35). In patients with NIU, systemic biologic therapy was associated with higher risks of serious infections and hematologic cytopenias compared with no systemic treatment, while demonstrating a broadly comparable five-year safety profile to conventional immunomodulatory therapy. These findings support guideline-concordant stepwise immunosuppression and underscore the importance of individualized risk assessment, infection surveillance, and hematologic monitoring for patients requiring systemic therapy.