Abstract
Background/Aims: Autoimmune-related events following anti-tumor necrosis factor alpha (anti-TNF-α) therapy are increasingly reported, but population-level data on new-onset autoimmune disease in inflammatory bowel disease (IBD) remain limited. We evaluated whether anti-TNF-α exposure is associated with autoimmune disease development in IBD. Methods: We conducted a nationwide population-based case-control study using data from the Korean National Health Insurance Service database (2004–2018). Patients with IBD who developed new-onset autoimmune diseases, including psoriasis, interstitial lung disease (ILD), systemic lupus erythematosus, systemic vasculitis, and central nervous system disorders, were matched 1:1 to controls by age, sex, diagnosis year, and IBD subtype. Logistic regression with propensity score matching and spline modeling was used to assess associations, including subgroup and sensitivity analyses. Results: Among 8,586 matched pairs, anti-TNF-α therapy was associated with increased risks of autoimmune disease (adjusted odds ratio [aOR], 1.65), particularly psoriasis (aOR, 1.58) and ILD (aOR, 1.88). A non-linear dose–response relationship was observed: the risk rose sharply at early exposure, plateaued at approximately 30 prescriptions, and gradually declined beyond 64. This association remained regardless of prior immunosuppressant use and was attenuated but significant in immunosuppressant users with psoriasis. No significant associations were found for systemic lupus erythematosus, central nervous system disorders, or vasculitis. Patients receiving prolonged concomitant therapy ( ≥ 90 days) showed increased risk (aOR, 1.43). Monotherapy showed a non-significant trend (aOR, 1.19). Conclusions: Anti-TNF therapy for IBD is associated with an increased risk of developing new-onset autoimmune diseases, especially psoriasis and ILD. Careful monitoring is warranted, particularly in patients receiving prolonged or combined immunosuppressive therapies.