The Impact of Methotrexate on Cardiovascular Outcomes in Psoriasis: A Systematic Review and Meta‐Analysis

Background Psoriasis is a chronic immune‐mediated inflammatory disease with a global prevalence of 2%–3% and 1.3% in Brazil. It is associated with comorbidities such as obesity, hypertension, and diabetes, all of which contribute to increased cardiovascular risk due to systemic inflammation and endothelial dysfunction. Methotrexate (MTX), a commonly used treatment for psoriasis, may influence cardiovascular outcomes through its anti‐inflammatory effects. Objectives To evaluate the impact of methotrexate on cardiovascular outcomes in patients with psoriasis, particularly its potential to reduce cardiovascular risk by controlling systemic inflammation. Methods A systematic review was conducted according to PRISMA guidelines. Searches were performed in PubMed, Cochrane, Embase, and Web of Science databases. Eligible studies assessed the effects of methotrexate on cardiovascular outcomes in psoriasis patients. Case reports and narrative reviews were excluded. Study quality was assessed using the RoB‐2 and GRADE tools. From 143 initially identified records, four studies met the inclusion criteria. Meta‐analyses using fixed‐effects and random‐effects models were conducted to estimate pooled odds ratios (ORs). Results Under the fixed‐effects model, methotrexate was associated with a significant reduction in cardiovascular risk (OR = 0.62; 95% CI: 0.57–0.68). However, due to high heterogeneity, the random‐effects model yielded nonsignificant results (OR = 0.86; 95% CI: 0.54–1.35). The incidence of cardiovascular events was similar between the methotrexate (3.6%) and control (3.7%) groups. Conclusions Methotrexate shows promise in reducing cardiovascular risk in psoriasis patients, likely due to its anti‐inflammatory properties. It appears to be a safer option compared to agents such as retinoids. Nonetheless, the high heterogeneity and methodological limitations of available studies hinder definitive conclusions. Further research should prioritize standardized outcome measures, comparisons with biologics, and individualized therapeutic approaches. PROSPERO Registration Number: CRD42024575673.