Abstract
BACKGROUND: Psoriasis is associated with various cardiovascular diseases (CVDs). The aim of this study was to compare the risk of CVD in patients with psoriasis who were prescribed biologics or oral therapies, and to assess the association between different classes of biologics and CVD risk. METHODS AND FINDINGS: This retrospective cohort study utilized the TriNetX Global Collaborative Network (2014-2025). Patients with psoriasis newly prescribed biologics (BIO-cohort) and those newly initiating oral anti-psoriatic drugs without biologic exposure (Non-BIO-cohort) were enrolled. A propensity score-matched analysis was conducted, accounting for age, sex, race, comorbidities, body mass index, serum lipid profile, and inflammatory marker levels. Cardiovascular risk was compared between the BIO- and Non-BIO-cohorts using Cox regression to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). After matching, each cohort comprised 12,732 patients, with approximately 50% being female, a mean age of 57 years, and 55% identifying as White. The 5-year cumulative incidence of any CVDs was significantly lower in the BIO-cohort (10.68%; 95% CI [10.03%, 11.36%]) than in the Non-BIO-cohort (16.17%; 95% CI: [15.34%, 17.05%]) (p < 0.001). The BIO-cohort had attenuated risks of any CVDs (HR 0.621; 95% CI [0.571, 0.676]), cerebrovascular diseases (HR 0.616; 95% CI [0.519, 0.731]), arrhythmias (HR 0.632; 95% CI [0.565, 0.706]), inflammatory heart diseases (HR 0.566; 95% CI [0.360, 0.891]), ischemic heart diseases (HR 0.579; 95% CI [0.465, 0.721]), heart failure (HR 0.637; 95% CI [0.521, 0.780]), non-ischemic cardiomyopathy (HR 0.654; 95% CI [0.466, 0.918]), thrombotic disorders (HR 0.570; 95% CI [0.444, 0.733]), peripheral arterial occlusive diseases (HR 0.501; 95% CI [0.383, 0.656]), and major adverse cardiac events (HR 0.697; 95% CI [0.614, 0.792]). Receiving only anti-tumor necrosis factor (TNF)-α (HR 0.886; 95% CI [0.807, 0.973]), anti-interleukin (IL)-17 (HR 0.724; 95% CI [0.599, 0.875]), or anti-IL-23 (HR 0.739; 95% CI [0.598, 0.914]) was associated with reduced risks of any CVDs, whereas no significant association was observed for only anti-IL-12/23 (HR 0.915; 95% CI [0.742, 1.128]). This risk reduction remained consistent across various subgroups, including age (≤45 or >45 years), sex (male or female), regions of research data (the United States, Europe, Middle East and Africa, and Asia-Pacific), and comorbidities (psoriatic arthritis, hypertension, diabetes, hyperlipidemia, overweight or obesity). Eight sensitivity analyses, such as extending the washout period or tightening medication definitions, validated our findings. The main limitation of our study is the observational design, which can only establish associations, not causation. CONCLUSIONS: Patients with psoriasis prescribed biologics exhibited a lower risk of CVDs versus those on oral therapy. Anti-TNF-α, anti-IL-17, and anti-IL-23 were associated with decreased cardiovascular hazards, while anti-IL-12/23 was not.