Association of autoimmune diseases with biologic agents targeting type 2 immunity: An observational study using a claims database

Abstract Background Biologic agents targeting type 2 immunity (anti‐type 2 agents) have been implicated in the risk of autoimmune diseases. This study aimed to assess the association between anti‐type 2 agents and the risk of developing autoimmune diseases. Methods This hypothesis‐generating, retrospective cohort, nested case‐control (NCC) study utilized a large claims database in Japan. Patients diagnosed with bronchial asthma, atopic dermatitis, chronic urticaria, or eosinophilic chronic rhinosinusitis between April 2018 and August 2024 were included. The exposures of interest were anti‐interleukin (IL)‐5, anti‐IL‐4/13, and anti‐IgE agents. The study outcomes included 11 autoimmune diseases and their composite. The risk of developing autoimmune diseases was assessed using two statistical models: NCC analysis and the time‐dependent Cox proportional hazard model. Results A total of 886,908 patients were included, with a median age of 42.0 years (interquartile range: 32.0, 52.0 years). The use of the anti‐IL‐5 agents and anti‐IgE agents showed consistent associations with the composite outcome: adjusted relative risk (RR) = 2.50 (95% confidence interval [CI]: 1.35–4.64) in NCC and RR = 3.02 (95% CI: 1.86–4.90) in Cox, and RR = 2.25 (95% CI: 1.37–3.67) in NCC and RR = 2.33 (95% CI: 1.61–3.39) in Cox, respectively. Regarding individual outcomes, rheumatoid arthritis and systemic lupus erythematosus were associated with the use of anti‐IL‐5 agents. In patients with atopic dermatitis, patients treated with anti‐IL‐4/13 exhibit a reduced occurrence of psoriasis. Conclusion The study provides valuable insights into the association between anti‐type 2 agents and autoimmune diseases in real‐world clinical practice, although causal interpretation requires further investigation.