Patients with psoriasis who are treated with methotrexate (MTX) show a reduced incidence of metabolic syndrome and better cardiometabolic profiles, according to a study presented at AAD 2026.
“MTX use in psoriasis was safe and associated with a lower prevalence of metabolic syndrome and improved cardiometabolic profiles, supporting its potential cardioprotective role,” said lead study author Dr Achala Liyanage, Faculty of Medicine, University of Ruhuna, Sri Lanka. “Larger longitudinal studies are needed to confirm long-term cardiovascular (CV) benefits.”
Liyanage and colleagues conducted this comparative cross-sectional study in dermatology clinics of three tertiary care hospitals in Southern Sri Lanka to evaluate the effect of MTX on CV risk profiles and treatment safety in patients with psoriasis. They compared 80 patients on MTX for ≥3 months with 80 MTX-naïve participants, matched for disease severity using the Psoriasis Area and Severity Index (PASI).
Liyanage and her team assessed the risk of CV events among patients using lipid profile, fasting blood sugar (FBS), high-sensitivity C-reactive protein (hs-CRP), carotid intima‒media thickness (CIMT), and Framingham Risk Score (FRS). They also recorded adverse events (AEs) associated with the use of MTX.
Age and PASI did not significantly differ between the MTX-treated and MTX-naïve groups, but the latter involved more males and smokers and had higher comorbidity. Despite having similar PASI, those in the MTX group had a greater body surface area involvement (p=0.026). [AAS 2026, abstract 70550]
Furthermore, psoriasis patients treated with MTX demonstrated significantly lower levels of FBS, triglycerides (TG), and very-low-density lipoprotein (VLDL; p<0.05 for all), as well as a lower prevalence of metabolic syndrome (31.2 percent vs 50.0 percent; p=0.016), than MTX-naïve participants. No significant between-group differences were seen in hs-CRP, CIMT, or FRS.
In terms of safety, the use of MTX did not result in any adverse hematologic or hepatic effects.
“Psoriasis patients receiving MTX showed a lower prevalence of metabolic syndrome, diabetes, hypertriglyceridaemia, and hypertension, together with lower FBS, TG, and VLDL levels, indicating a reduced CV risk compared to non-MTX users,” Liyanage said.
“As CV risk factors tend to cluster and exert a multiplicative effect, their concurrent reduction may have meaningful clinical implications,” she added.
Cardioprotective benefits
In previous studies, MTX appeared to provide cardioprotection through the suppression of proatherogenic cytokines and the enhancement of antiatherogenic pathways. However, these findings, particularly those on lipid profiles, remain inconsistent. [N Engl J Med 2019;380:752-762; Clin Epidemiol 2021;13:693-705]
In addition, large clinical trails fell short of demonstrating a clear reduction in CV events, and MTX-related hyperhomocysteinaemia could offset the potential benefits. [J Eur Acad Dermatol Venereol 2014;29:1128-1134; Med J Armed Forces India 2024;80:S174-S179]
“Given the cross-sectional design and small sample size, causal inference is not possible, and the observed differences cannot be attributed exclusively to MTX,” Liyanage said. “Nevertheless, these findings support the need for larger prospective studies to clarify MTX’s CV effects in psoriasis.”