Systemic Treatment and Narrowband Ultraviolet B Differentially Affect Cardiovascular Risk Markers in Psoriasis

Sigurdardottir G, Ekman AK, Ståhle M, Bivik C, Enerbäck C

J Am Acad Dermatol. 2014;70:1067-1075

Study Summary

Over the past decade, the concept of psoriasis as a systemic rather than primarily cutaneous inflammatory disease has taken root, thanks to pivotal studies linking psoriasis to cardiovascular disease and the metabolic syndrome.[1,2,3] Prior studies have shown that biomarkers of cardiovascular risk, such as proinflammatory cytokines and adipokines, are elevated in patients with psoriasis, and that serum levels of these markers correlate with psoriasis severity.[4] Furthermore, continuous systemic therapy for severe psoriasis can reduce adipokine levels.[5]

Building on this foundation, Sigurdardottir and colleagues investigated how serum levels of 6 different markers of cardiovascular risk change in response to therapy with narrow-band ultraviolet B (NB-UVB) vs the tumor necrosis factor (TNF)-alpha inhibitor etanercept. This nonrandomized study analyzed the plasma of 28 patients with psoriasis compared with 28 age- and sex-matched controls.

The investigators also quantified the serum levels of 6 cardiovascular risk biomarkers in patients with psoriasis before and after 12 weeks of therapy with either NB-UVB (n = 21) or etanercept (n = 20). Inflammatory markers were vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, matrix metalloproteinase-9, myeloperoxidase, and total plasminogen activator inhibitor-1.

The investigators observed the following:

Five out of 6 cardiovascular risk biomarkers showed statistically significant elevations in patients with psoriasis vs controls (and vascular cell adhesion molecule-1 showed a "tendency toward elevation"). The serum levels of 4 of these biomarkers correlated with body mass index and waist-to-hip ratio, measurements that are indicators of the metabolic syndrome. Etanercept significantly reduced the levels of all biomarkers. Patients treated with NB-UVB showed no reductions in any biomarkers, despite clinical improvement in psoriasis.

Viewpoint

A lethal cocktail of proinflammatory cytokines, adipokines, and metalloproteinases increases the risk for cardiovascular disease. Many of these biomarkers are also elevated in patients with the metabolic syndrome or psoriasis, with higher levels found in those with more severe skin and joint psoriasis.

Because TNF-alpha is a potent inflammatory cytokine, TNF-alpha inhibitors, such as etanercept and adalimumab, suppress psoriasis by inhibiting the proinflammatory cytokine cascade. As others have shown, this may in turn reduce the risk for cardiovascular disease.[6,7]

Sigurdardottir and colleagues showed an impressive reduction in all 6 measured proinflammatory markers after 12 weeks of etanercept therapy for psoriasis. In contrast, NB-UVB phototherapy failed to reduce the serum levels of any of these markers.

This study was too small to yield conclusive results. Nevertheless, Sigurdardottir and colleagues provide intriguing evidence that TNF-alpha inhibition may yield benefits for psoriasis patients that are more than skin deep. It should be emphasized, however, that cardiovascular risk "biomarkers" are just that: markers that predict a higher risk for cardiovascular disease. Hence, treatments that reduce these markers, especially over a short time window such as in the above study, will not necessarily improve morbidity or mortality outcomes.

Controlled clinical trials are needed to address many key questions that remain. For instance:

Do TNF-alpha inhibitors reduce the risk for cardiovascular disease, including specific clinically meaningful endpoints (death, incidence of myocardial infarction, stroke)? If so, is this benefit cumulative over time? What length of treatment is needed? Do all TNF-alpha inhibitors confer a similar benefit? What about other biologic agents, such as those that target interleukin-12/23 and interleukin-17? And what about other systemic therapies (cyclosporine, methotrexate)? Can TNF-alpha blockade reverse some of the signs and symptoms of the metabolic syndrome or reduce associated morbidities?

Even without these definitive answers, clinicians should consider the potential reduction in cardiovascular risk when weighing the risks and benefits of starting TNF-alpha therapy.

Abstract