Cardiovascular Risk Associated with Methotrexate versus Retinoids in Patients with Psoriasis: A Nationwide Taiwanese Cohort Study

Abstract

Purpose Psoriasis is an inflammatory disease associated with cardiovascular disease. Methotrexate (MTX) is a first-line systemic anti-psoriatic agent that may also protect against cardiovascular disease. We examined the cardiovascular risks among patients with psoriasis who were receiving MTX or the comparator, retinoids. Patients and Methods We analysed data from the Taiwanese National Health Insurance database. The primary outcome was a composite of hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality (composite cardiovascular outcome). Propensity score-weighted analyses were used to evaluate patients who were followed from therapy initiation to the earliest instance of outcome occurrence, insurance disenrollment, death or study termination. Results We identified 13,777 patients who received MTX and 6020 patients who received retinoids from 2000 to 2012. Compared to retinoids, MTX was associated with lower crude incidences of cardiovascular outcomes, hospitalisation for ischaemic heart disease, ischaemic stroke and all-cause mortality. In intention-to-treat analyses, MTX was associated with lower risks of composite cardiovascular outcomes (adjusted hazard ratio [HR]: 0.84, 95% confidence interval [CI]: 0.76–0.94), ischaemic heart disease (HR: 0.87, 95% CI: 0.71–1.06), ischaemic stroke (HR: 1.06, 95% CI: 0.89–1.27) and all-cause mortality (HR: 0.75, 95% CI: 0.66–0.85). Similar results were found in as-treated analyses. Conclusion In this nationwide cohort of patients with psoriasis, compared to retinoids, MTX was associated with a modestly lower risk of cardiovascular events.

Association between cardio‐cerebrovascular disease and systemic antipsoriatic therapy in psoriasis patients using population‐based data: A nested case–control study

“…Based on the presumed association between psoriasis and CCVD, several studies explored the effects of systemic antipsoriatic therapies on CCVD risk in psoriasis patients. Regarding conventional antipsoriatic agents, a few studies demonstrated the protective effect of methotrexate against CCVD development 19,20 . Moreover, some data indicated a cardioprotective effect of biologics in psoriasis patients 13,21 .…”

“…Wu et al found that anti‐TNF‐treated psoriasis patients had a decreased incidence of myocardial infarction as compared to those treated with only topical agents 12 . Despite the reported cardioprotective effects of a few treatment modalities for psoriasis in these studies, they had some limitations, including the enrollment of patients with rheumatoid arthritis as well as psoriasis patients, 19 the focus on the use of a single systemic antipsoriatic agent for a short treatment duration, or limited follow‐up periods 12,13,20,21 . Considering real‐world characteristics of psoriasis treatment, such as long‐term treatment, rotational or sequential treatment using various treatment modalities, and intermittent treatment to avoid the side effects during long‐term use of a single antipsoriatic treatment, 22–24 the cardioprotective effects of systemic antipsoriatic therapies in psoriasis patients can be properly investigated through an analysis that incorporates all systemic antipsoriatic therapies used in each patient.…”

“…Previous studies compared the cardioprotective effects of various systemic antipsoriatic therapies to determine the appropriate treatment modality for psoriasis patients. Tsai et al performed a head‐to‐head comparison between methotrexate and retinoid in CCVD risk and reported that methotrexate was associated with a reduced CCVD risk as compared to retinoid 20 . Additionally, recent studies showed a cardioprotective effect of biologics in psoriasis patients.…”

“…Regarding conventional antipsoriatic agents, a few studies demonstrated the protective effect of methotrexate against CCVD development. 19,20 Moreover, some data indicated a cardioprotective effect of biologics in psoriasis patients. b OR for a 10% increase of PTP.…”

Beyond the Skin Plaques: Psoriasis and Its Cardiovascular Comorbidities

“…In the same study by Lan et al, retinoid therapy showed no variability in the risk of cerebrovascular disease development [ 71 ]. Retinoids have been shown to be less effective in yet another cohort study by Tsai et al, who found that there was a lower incidence of adverse cardiovascular outcomes, ischemic stroke, ischemic heart disease, and total mortality with methotrexate when compared to retinoids [ 73 ]. From the calcineurin inhibitor family, the T cell-inhibiting drug cyclosporine is also used for psoriasis treatment [ 11 ].…”