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

Purpose: To compare 5-year systemic complication risks in noninfectious uveitis (NIU) patients treated with systemic biologic versus conventional therapy.

Design: Multicenter, retrospective clinical cohort study.

Participants: Adult patients (≥18 years old) with NIU from the TriNetX Collaborative Network.

Methods: We identified patients with NIU. We assembled propensity score-matched comparisons: biologic therapy versus no systemic therapy (n = 6896 each) and biologic versus conventional therapy with corticosteroids matched (n = 5994 each) between January 1, 2005, and January 1, 2024. A prespecified subgroup analysis of Analysis 2 restricted to patients receiving combination biologic + conventional therapy versus conventional therapy alone (n = 3653 each) was also conducted. We used time-to-event analyses to identify incidence of systemic complications.

Main outcome measures: Incidence of serious infections, hematologic cytopenias, heart failure, thromboembolic events, diabetes mellitus, malignancy, psychiatric illness, all-cause hospitalization, and all-cause mortality.

Results: After propensity score matching, cohorts were balanced on all measured covariates (all standardized mean differences [SMDs] <0.1). Compared with no systemic therapy, biologic treatment was associated with higher 5-year risks of serious infections, including pneumonia (hazard ratio [HR], 1.41, 95% confidence interval [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 5-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).

Conclusions: 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 5-year safety profile broadly comparable 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.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.