Network meta-analysis of immunomodulatory therapies for Behçet's disease-associated uveitis: comparative evaluation of safety and efficacy profiles

Abstract

Purpose: To systematically evaluate and compare the efficacy and safety profiles of various immunomodulatory therapies for Behçet's Disease-associated uveitis (BDU) through network meta-analysis, providing evidence-based guidance for clinical practice.

Methods: We conducted a comprehensive systematic review following PRISMA guidelines. Electronic databases (PubMed, Cochrane CENTRAL, Scopus, Google Scholar) were searched for studies published between 2000 and 2025. Randomized controlled trials and observational studies comparing immunomodulatory treatments for BDU were included. Risk of bias was assessed using RoB2 and ROBINS-I tools. Network meta-analysis was performed using R version 4.4.1, with treatments ranked via Surface Under the Cumulative Ranking Curve Analysis (SUCRA). Efficacy was defined as the achievement of ocular inflammatory remission and visual acuity improvement. Benefit-risk profiles incorporated therapeutic effectiveness weighted against treatment-related adverse events. Pairwise comparisons and comprehensive safety analyses were conducted.

Results: Seventeen studies comprising 1,339 patients were included after screening 714 records. The network meta-analysis revealed that IL-1 inhibitors (SUCRA 75.2%) and TNF inhibitors (SUCRA 74.0%) ranked highest in efficacy for controlling inflammation and preventing relapses. Conventional treatments ranked lowest (SUCRA 14.4%). Safety analysis demonstrated that IL-1 inhibitors had the most favorable profile (serious adverse events: 2.4%, treatment discontinuation: 3.6%), while cyclophosphamide showed the least favorable profile (adverse events: 64%, infections: 24%, discontinuation: 16%). TNF inhibitors achieved the highest benefit-risk balance score (77/100). Publication bias assessment revealed potential bias in older, non-randomized studies.

Conclusions: This network meta-analysis provides compelling evidence that biologics, particularly TNF and IL-1 inhibitors, offer superior efficacy and safety profiles compared to conventional immunosuppressants for BDU. The findings suggest a treatment paradigm where TNF inhibitors appeared to rank highly in efficacy; however, without subgroup analysis, this observation remains exploratory. Treatment selection should be individualized based on disease severity, patient-specific factors, and risk profiles. These results provide a comprehensive evidence-based framework for clinical decision-making in BDU management.

Keywords: Behçet's disease; IL-1 inhibitors; Immunomodulatory therapies; Network meta-analysis; TNF inhibitors.