Effect of tumor necrosis factor inhibitors on risk of depression in patients with ankylosing spondylitis: a nationwide propensity score-matched cohort study

Objective Depression is a significant comorbidity in patients with ankylosing spondylitis (AS), contributing substantially to the overall disease burden. While studies have suggested that tumor necrosis factor inhibitors (TNFi) may alleviate depressive symptoms, their effect on the incidence of depression remains unclear. We aimed to investigate the effect of TNFi on the incidence of depression in patients with AS. Methods This was a nationwide propensity score-matched cohort study, using the Korean nationwide claims database. A cohort of patients with AS with no history of depression was derived from the database. 1:1 propensity score-matched TNFi exposure (n = 4,284) and TNFi non-exposure (n = 4,284) groups were constructed for analysis. The index date was the TNFi initiation date for TNFi exposure group and a comparable index date based on matched disease duration for TNFi non-exposure group. Patients were followed from the index date to depression occurrence or June 2024, whichever came first. The association between TNFi exposure and risk of depression was assessed using multivariable stratified Cox regression analysis. Results The incidence rates of depression in TNFi exposure and TNFi non-exposure groups were 1.39 (95% confidence interval [CI] 1.28–1.51)/100 person-years and 1.78 (95% CI 1.65–1.91)/100 person-years, respectively. In the multivariable stratified Cox regression analysis, TNFi exposure was associated with a significantly lower risk of depression (adjusted hazard ratio 0.82, 95% CI 0.72–0.92, p= 0.001). Conclusion TNFi exposure was associated with a lower incidence of depression in patients with AS, suggesting a potential mental health benefit of TNFi, extending beyond symptom control to prevention of new-onset depression.