Comparative risk of uveitis with Janus kinase inhibitors versus tumor necrosis factor inhibitors in ankylosing spondylitis and psoriatic diseases: a target trial emulation study.

Objectives: To compare the risk of incident uveitis among patients with axial spondyloarthritis initiating treatment with Janus kinase inhibitors (JAKi) versus tumor necrosis factor inhibitors (TNFi). Methods: We conducted an emulated target trial using real-world electronic health records from the TriNetX US Collaborative Network. Adults with ankylosing spondylitis (AS), psoriasis (PsO), or psoriatic arthritis (PsA) who newly initiated a JAKi or a TNFi between January 1, 2016, and December 31, 2023, were identified. Patients were stratified into JAKi and TNFi cohorts based on initial treatment exposure. Propensity score matching (1:1) was performed to balance baseline demographics, comorbidities, prior medication use, and laboratory values. Cox proportional hazards models were used to estimate hazard ratio (HR) and 95% confidence interval(CI) for the development of incident uveitis, with TNFi as the reference. Kaplan-Meier analysis was conducted to compare the 9-year cumulative incidence of uveitis between cohorts. The primary outcome was incident uveitis following initiation of therapy, with follow-up extending up to nine years. Results: Among 697,850 patients identified, 5,874 were included in each group after 1:1 propensity score matching. JAKi use was associated with a lower risk of incident uveitis compared with TNFi (HR = 0.630; 95% CI, 0.418-0.948). These findings remained consistent after further adjustment for comorbidities, medications, and laboratory data. Subgroup analyses showed a consistent protective association in older patients (≥ 51 years: HR = 0.43, 95% CI = 0.24-0.79), White individuals (HR = 0.59, 95% CI = 0.38-0.93), and those with elevated inflammatory markers (CRP ≥ 3 mg/L: HR = 0.50, 95% CI = 0.26-0.96; ESR ≥ 20 mm/h: HR = 0.41, 95% CI = 0.19-0.87). The reduced risk persisted regardless of concomitant use of conventional synthetic DMARDs (with csDMARDs: HR = 0.50, 95% CI = 0.28-0.92; without csDMARDs: HR = 0.56, 95% CI = 0.33-0.94). Conclusions: In this large-scale, real-world cohort study, JAKi therapy was associated with a significantly reduced risk of incident uveitis compared to TNFi therapy in patients with AS, PsO, or PsA. These findings suggest a potential role for JAKi in mitigating ocular inflammation in this population. Further prospective studies and randomized controlled trials are warranted to validate these results and inform future clinical guidelines.