Multiple sclerosis disease modifying therapy (DMT) and uveitis risk: systematic review and meta-analysis

Background To systematically assess the impact of disease-modifying therapy (DMT) on the risk of uveitis in patients with multiple sclerosis (MS) and to investigate potential variations among different DMT types, MS types, and clinical characteristics. Methods A systematic search was conducted across PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP databases from the self-established database up to September 2025. This search aimed to identify randomized controlled trials, cohort studies, and observational studies that reported the incidence of uveitis following disease-modifying therapy (DMT) in patients with multiple sclerosis (MS). Meta-analysis was performed using Stata 18.0. Bivariate outcomes were expressed as odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was evaluated using the I² test, applying a random effects model when I² was ≥ 50%. Publication bias was assessed through funnel plots and the Egger test, while sensitivity analysis was conducted using the leave-one-out method to confirm the stability of the results. Results A total of 8 studies (1 RCT, 7 observational studies) involving patients with multiple sclerosis (MS) from various regions were included. The pooled analysis indicated that disease-modifying therapy (DMT) significantly reduced the prevalence of uveitis (SMD = -0.42, 95% CI: -0.83 to -0.01, P  = 0.04). In the one-arm rate analysis, the combined prevalence was approximately 1% (95% CI: 0.00–0.01, I² = 88.09%). Subgroup analysis revealed that interferon beta and glatiramer acetate were associated with the highest risk of uveitis (~ 0.32), while fingolimod and rituximab were linked to the lowest risk (~ 0.01), with significant differences observed between groups ( P  < 0.01). Patients with relapsing-remitting multiple sclerosis (RRMS) and those experiencing relapses were at greater risk compared to individuals with primary progressive multiple sclerosis (PPMS) and de novo cases. The publication bias test indicated some bias; however, the results remained significant and stable after adjustment using the cut-and-complement method. Conclusion Significant differences exist in the risk of uveitis associated with various disease-modifying therapies (DMTs) in patients with multiple sclerosis (MS). Interferon beta may elevate this risk, whereas fingolimod and rituximab may confer protective effects. Clinicians should prioritize ocular safety when developing individualized treatment plans, particularly for individuals with a history of uveitis or those categorized as high-risk for ocular complications.