Arjun Mahajan

Objectives: To evaluate the long-term risks of liver disease among patients with psoriasis treated with interleukin 23 inhibitors (IL-23i), IL-17i and tumour necrosis factor-alpha inhibitors (TNFi), compared with each other and with systemic therapy-naïve (STN) patients. Design: Large-scale emulated target trials using propensity score matched cohorts within an intention-to-treat framework. Setting: Electronic medical record data from 131 healthcare organisations within the TriNetX research network (2017–2025). Participants: 24 920 adults with psoriasis treated with IL-23i, IL-17i or TNFi and STN controls. Interventions: Exposure to IL-23 inhibitors, IL-17 inhibitors or TNF inhibitors compared with STN management. Main outcome measures: 4-year incidence of any liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD) and liver fibrosis and cirrhosis. Results: Compared with STN patients, IL-23i treatment (5247 matched pairs) was associated with lower risks of any liver disease (HR 0.74; 95% CI 0.63 to 0.87), MASLD (HR 0.84; 95% CI 0.73 to 0.91) and fibrosis or cirrhosis (HR 0.81; 95% CI 0.70 to 0.92). IL-17i (4579 matched pairs) and TNFi (15 007 matched pairs) treatment were not associated with significant differences in these outcomes. No significant differences were observed in head-to-head comparisons between biologic classes. Conclusions: IL-23i therapy was associated with lower risks of incident liver disease and related outcomes in psoriasis, suggesting biologic selection may influence long-term hepatic risk, warranting further investigation into underlying mechanisms and the potential benefit of early intervention.