ABSTRACT
BACKGROUND: Methotrexate (MTX) is a folate analogue used in the treatment of moderate to severe psoriasis and rheumatoid arthritis (RA). It oppositely affects inflammation and hyperhomocysteinemia-two independent risk factors for vascular disease. To date, there are no published reports evaluating the impact of these potentially paradoxical action of MTX. OBJECTIVE: The purpose of this study was to evaluate the effect of MTX therapy on the incidence of vascular disease in patients with psoriasis and RA. METHODS: We conducted a retrospective cohort study in which we analyzed computerized records of 7,615 outpatients diagnosed with psoriasis and 6,707 with RA at the Veterans Integrated Service Network 8. RESULTS: Patients prescribed MTX therapy had a significantly reduced risk of vascular disease compared to those who were not prescribed MTX (psoriasis: RR = 0.73, 95% CI = 0.55-0.98; RA: 0.83, 0.71-0.96). This reduction was most evident for patients prescribed a low cumulative dose of MTX (psoriasis: RR = 0.50, 95% CI = 0.31-0.79; RA = 0.65, 0.52-0.80). Concomitant use of folic acid (FA) with MTX also reduced the incidence of vascular disease in patients prescribed MTX (psoriasis: RR = 0.56, 95% CI = 0.39-0.80; RA: 0.77, 0.38-1.56). CONCLUSIONS: MTX therapy reduced the incidence of vascular disease in veterans with psoriasis or RA. Low to moderate cumulative dose appears more beneficial than the higher dose. We hypothesize that this effect is caused by its anti-inflammatory properties. In addition, a combination of MTX and FA led to a further reduction in the incidence of vascular disease.