Comparative long-term outcomes of conventional immunomodulatory therapy, biologic agents, and combination therapy in chronic uveitis

BACKGROUND: Chronic non-infectious uveitis can lead to vision loss if not adequately controlled. Thus, steroid-sparing immunomodulatory therapy (IMT) is often required to achieve and maintain disease quiescence. It is unclear if biologic agents inhibiting tumor necrosis factor alpha (TNF-α) provide superior control of chronic uveitis compared to conventional IMTs on their own or as combination therapy. METHODS: This is a multicenter retrospective cohort study using the TriNetX US Collaborate network. Adult patients (≥18 years) with chronic non-infectious uveitis who achieved steroid-sparing quiescence on IMT were included. Patients were grouped by initial maintenance with conventional IMT (methotrexate, mycophenolate mofetil, or azathioprine), biologic TNF-α inhibitor (adalimumab or infliximab) or combination therapy (both conventional IMT and biologic agent), and the incidence of flares over 6, 12, 18 and 24 months of follow-up were analyzed. Outcomes were compared between groups using paired chi-squared tests on propensity score matched cohorts with relative risk (RR) and 95% confidence intervals calculated for each outcome. RESULTS: A total of 2,912 patients on conventional IMT, 736 patients on biologic therapy and 1,313 on combination therapy met the definition of steroid-sparing control. Patients on combination therapy had significantly lower rates of flares as compared to those on conventional IMT at 6 months (RR 0.53; p = 0.0070), 12 months (RR 0.52; p = 0.0011), 18 months (RR 0.56; p = 0.0022) and 24 months (RR 0.56; p = 0.0012). No difference in the rate of flares was found between combination versus biologic therapy, or conventional IMT versus biologic therapy at 6-, 12-, 18- and 24 months. Patients initially treated with conventional IMT had higher rates of augmentation or switching to biologic therapy at 12 months (RR 1.74; p = 0.0386), 18 months (RR 1.65; p = 0.0219) and 24 months (RR 1.65; p = 0.0114). CONCLUSION: The current study indicates that for patients with chronic uveitis who achieve steroid-sparing control on IMT, those treated with a combination of a conventional IMT and a biologic TNF-α inhibitor have a lower risk of disease activation as compared to those on conventional IMT.