Comparative Efficacy and Safety of Systemic Immunomodulatory Therapies for Non-Infectious Uveitis: A Systematic Review With Pairwise and Network Meta-Analyses.

INTRODUCTION

Non-infectious uveitis (NIU) is a chronic immune-mediated ocular inflammatory disease that may cause irreversible visual impairment. The comparative efficacy and safety of systemic immunomodulatory therapies, including conventional agents and biologics, remain incompletely defined. This systematic review and network meta-analysis evaluated systemic immunosuppressive therapies for NIU.

METHODS

PubMed/MEDLINE, Cochrane CENTRAL, Scopus and Web of Science Core Collection were searched from inception to May 2, 2026. Randomized controlled trials and prospective comparative cohort studies evaluating systemic immunomodulatory or biologic therapies for NIU were included. The primary efficacy outcome was treatment failure. Safety outcomes included mortality, urinary tract infection, upper respiratory tract infection, injection-site reactions, ocular hypertension, macular edema, and headache. Random-effects pairwise meta-analysis and frequentist network meta-analysis were performed using risk ratios (RRs) with 95% confidence intervals (CIs).

RESULTS

Seven studies including 992 participants were included; six were randomized controlled trials and one was a prospective cohort. In the pairwise meta-analysis, adalimumab significantly reduced treatment failure compared with placebo (RR, 0.67; 95% CI, 0.58-0.78; p < 0.0001; I² = 28.1%). The mortality estimate was inconclusive (RR, 3.80; 95% CI, 0.42-34.15), with three deaths in the adalimumab groups and none in the placebo groups. Adalimumab was associated with a higher risk of injection-site reactions than placebo (RR, 2.67; 95% CI, 1.73-4.12). Network meta-analysis showed no significant differences for most safety outcomes, including upper respiratory tract infection, ocular hypertension, macular edema, and headache. Infliximab showed an imprecise urinary tract infection signal versus placebo (RR, 40.98; 95% CI, 1.82-922.17), based on sparse events and one nonrandomized comparison.

CONCLUSION

Adalimumab provides the most consistent evidence for reducing treatment failure in NIU. Comparative safety estimates, particularly for infliximab, remain uncertain and hypothesis-generating. Larger, long-term, head-to-head trials are required.