Trends in immunomodulatory therapy for the treatment of chronic uveitis in the United States

Chronic uveitis, a major cause of legal blindness in the United States, often requires long-term immunomodulatory therapy (IMT). This study aims to characterize trends in systemic IMT use among adults with chronic uveitis in United States from 2005 to 2025. This cross-sectional time-series study used the TriNetX Network to analyze adults (ages ≥ 18) with chronic, non-infectious uveitis treated with methotrexate, mycophenolate, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, adalimumab, infliximab and/or etanercept. Data was grouped into consecutive 3-year intervals, and Cochran–Armitage tests assessed changes in the proportion of patients treated with each medication. The total population included 12,035 adult patients. Academic and non-academic institutions shared similar trends in IMT usage. Overall, there was a reduction in the proportion of patients on methotrexate (44.2% in 2005–2007 to 37.6% in 2023–2025, p < 0.0001), azathioprine (15.1% in 2005–2007 to 6.7% in 2023–2025, p < 0.0001), cyclophosphamide (2.5% in 2011–2013 to 0.8% in 2023–2025, p < 0.0001), infliximab (18.6% in 2005–2007 to 14.1% in 2023–2025, p < 0.0001) and etanercept (9.0% in 2005–2007 to 2.0% in 2023–2025, p < 0.0001). Conversely, treatment with adalimumab rose markedly among patients with chronic uveitis (8.0% in 2005–2007 to 34.6% in 2023–2025; p < 0.0001). There was no change in the proportion of patients on mycophenolate (14.6% in 2005–2007 to 12.8% in 2023–2025; p = 0.5963). Key shifts in management of chronic uveitis include the emergence adalimumab as a key steroid sparing agent, the continued role of methotrexate as the first-line steroid-sparing agent, and a marked decline in the use of many older immunomodulatory therapies.