Systemic anti-inflammatory therapy and risk of major adverse cardiovascular events in patients with psoriasis: a population-based cohort study

Background Chronic inflammatory diseases are associated with an increased risk of major adverse cardiovascular events. Psoriasis represents a well-characterised inflammatory condition, yet the cardiovascular impact of different systemic anti-inflammatory treatment strategies in real-world practice remains incompletely defined. Purpose To evaluate the association between systemic treatment strategies for psoriasis and the risk of major adverse cardiovascular events, and to assess whether cardiovascular risk differs across biologic drug classes. Methods A retrospective population-based cohort study was conducted using electronic health records of adult patients with psoriasis who initiated systemic therapy between 2002 and 2024 and were free of prior cardiovascular events at treatment initiation. Two complementary analyses were performed: (1) comparison of methotrexate versus biologic monotherapy, and (2) comparison of tumour necrosis factor inhibitors (TNFi) versus non–tumour necrosis factor inhibitor biologics among biologic-treated patients. Inverse probability of treatment weighting (IPTW) was applied to balance baseline cardiovascular risk factors. Time-to-event analyses were performed using weighted Kaplan–Meier methods and Cox proportional hazards models. The primary outcome was incident major adverse cardiovascular events (MACE), defined as a composite of ischaemic heart disease, cerebrovascular accident, and all-cause mortality. Results The primary cohort included 5,884 patients (4,052 methotrexate initiators and 1,832 biologic initiators). During follow-up, 582 MACE events occurred among methotrexate users (14.3%) and 100 among biologic users (5.5%). Crude incidence rates were 21.0 and 9.9 events per 1,000 person-years, respectively (absolute rate difference 11.1; 95% confidence interval [CI] 8.51–13.68; p<0.001). After IPTW adjustment, biologic therapy was associated with a significantly lower risk of MACE compared with methotrexate (hazard ratio [HR] 0.72; 95% confidence interval 0.57–0.92; p=0.008). In a secondary analysis of 5,286 biologic-treated patients, no statistically significant difference in cardiovascular risk was observed between tumour necrosis factor inhibitors and non–tumour necrosis factor inhibitor biologics (HR 1.58; 95% CI 0.74–3.37; p=0.20). Conclusion In a large real-world cohort, initiation of biologic therapy was associated with a significantly lower risk of major adverse cardiovascular events compared with methotrexate. No significant differences in cardiovascular risk were observed across biologic classes. These findings support the relevance of systemic inflammation modulation in cardiovascular risk reduction and suggest that biologic therapy may offer superior cardiovascular protection over methotrexate in high-risk inflammatory states.