Long-term postmarketing safety of psoriasis treatments on autoimmune disease risk: a 15-year nationwide cohort study in Denmark

Background Psoriasis is a chronic immune-mediated skin disease, reported to affect approximately 2–3% of the global population, with prevalence in Denmark estimated at around 5%. Objectives To assess the long-term safety of interleukin (IL) inhibitors in relation ot secondary autoimmune diseases. Methods Among patients with psoriasis diagnosed between 1994 and 2023, a total of 36 155 were followed during their treatment exposure (2009–2023) using data from the Danish National Patient and Prescription Registries. Exposure groups included IL inhibitors, tumour necrosis factor (TNF)-α inhibitors, and nonbiologic treatments. Different analytical approaches used in the analyses included intention-to-treat (ITT), on-treatment (OT) and continuous index treatment estimands. Hazard ratios (HRs) were calculated using Cox regression models, and supplementary analyses examined prior autoimmune disease and psoriatic arthritis (PsA) status. Results IL inhibitors were consistently found to be associated with a lower risk of developing secondary autoimmune diseases. Based on the ITT estimand, TNF-α inhibitors were associated with a 54% increased risk [HR 1.54, 95% confidence interval (CI) 1.06–2.24] of selected autoimmune diseases. Based on the OT estimand, nonbiologic treatments were associated with an elevated risk (HR 1.57, 95% CI 1.01–2.42). Supplementary analyses including patient history of prior autoimmune disease and PsA status suggested effects in the same directions. Conclusions The present national population-based cohort study, which included all Danish patients diagnosed with psoriasis in hospital settings between 2009 and 2023, found that IL inhibitors were not associated with a higher risk of secondary autoimmune diseases than TNF-α inhibitors and nonbiologic treatments. These findings were observed regardless of patients’ pre-existing autoimmune comorbidities. Thus, IL inhibitors were not associated with a higher risk of developing subsequent autoimmune diseases, even among patients with existing autoimmune conditions. These findings may help inform clinicians’ treatment decisions.