Unravelling the Major Cardiovascular Risks of Systemic Psoriasis Medications: A Literature Systematic Review

ABSTRACT Background Psoriasis is a chronic inflammatory dermatological condition associated with an elevated risk of cardiovascular events (CVEs). Systemic therapies have transformed disease management, but their cardiovascular (CV) safety profiles remain incompletely understood and inconsistently reported. Objectives To systematically evaluate and synthesize current evidence on the CV risks of systemic psoriasis treatments, with particular attention to treatment‐specific effects, study design quality and consistency of CV outcome reporting. Methods Following PRISMA guidelines, we searched four major databases for studies published from January 2013 to August 2024. Eligible studies included randomized‐controlled trials (RCTs), registry‐based RCTs (rRCTs), cohort studies, pharmacovigilance analyses and systematic reviews/meta‐analyses reporting CVEs in adults treated with systemic psoriasis therapies. We used Cochrane Risk of Bias Tools (ROB 2) and Risk Of Bias In Non‐randomized Studies ‐ of Interventions (ROBINS‐1) to assess the quality of included citations. Results From 14,744 records, 195 studies involving 1,795,823 patients were included. Methotrexate (MTX) and tumour necrosis factor inhibitors (TNFi) consistently demonstrated CV protective effects, with reductions in myocardial infarction, stroke and CV mortality supported by high‐quality evidence. Interleukin‐17 (IL‐17) inhibitors showed neutral to potentially beneficial CV profiles in both RCTs and observational studies. In contrast, cyclosporine, retinoids and fumaric acid esters were associated with elevated CV risks, particularly in retrospective cohorts. Evidence for IL‐12/23 and IL‐23 inhibitors was mixed—short‐term trials indicated safety, but some real‐world and pharmacovigilance data raised concerns. Sensitivity analyses confirmed that conclusions were robust when allocated to studies with a low risk of bias and prespecified CV endpoints. Conclusions CV safety varies substantially among systemic psoriasis therapies. MTX and TNFi agents appear most favourable for patients at elevated CV risk. IL‐17 inhibitors may also be safe alternatives. Further long‐term, high‐quality studies are needed to clarify the safety of newer biologics and Janus kinase (JAK) inhibitors.