Liver disease risk in patients with psoriasis treated with biologics
Arjun Mahajan, Maureen Whittelsey, David Westfall Bates, Jeffrey A Sparks, Avery H LaChance, Sheela Reddy, Evan W PietteObjectives
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.