Real-world evidence for repurposing hydralazine as a potential epigenetic modulator for psoriasis: a 16-year retrospective nationwide cohort study

BACKGROUND: Dysregulated DNA methylation and hypertension (HTN) are closely associated with the development of psoriasis. However, the impact of the vasodilator hydralazine (HLZ), which also inhibits DNA methyltransferase, on psoriasis risk remains unclear. This study investigated the association of HLZ use with the risk of psoriasis and the severity of incident psoriasis. METHODS: This nationwide cohort study utilized data from the Taiwan Longitudinal Generation Tracking Database (2000–2015). We compared three propensity score-matched groups: patients with HTN treated with HLZ (HTN and HLZ cohort, n = 61,794), patients with HTN on other antihypertensives (HTN and non-HLZ cohort, n = 247,176), and patients without HTN (non-HTN cohort, n = 247,176). RESULTS: Patients with HTN using HLZ exhibited a lower risk of psoriasis than those using other antihypertensive agents [adjusted hazard ratio (aHR): 0.786, 95% CI: 0.535–0.930, p = 0.015]. Furthermore, the HTN and HLZ cohort was associated with a lower likelihood of requiring systemic treatment (aHR: 0.672, 95% CI: 0.522–0.894, p < 0.001) and linked to a lower risk of cause-specific mortality (aHR: 1.531 vs. 1.625, p < 0.001). CONCLUSIONS: In this large-scale observational study, HLZ use was associated with a lower risk and reduced severity of incident psoriasis in patients with HTN. While these findings cannot establish causality, they provide compelling real-world evidence to support further investigation into repurposing HLZ as a potential epigenetic modulator for psoriasis.