Efecto anti inflammatorio sistemico endotelial

Published in Dermatology

Journal Scan / Research · May 13, 2020

Differential Effects of Biologics on Psoriasis-Related Vascular Inflammation and Risk of Thrombosis

Journal of Investigative Dermatology

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• White blood cell samples from psoriasis patients treated with a TNF-α inhibitor (adalimumab), an IL-12/23 inhibitor (ustekinumab), or an IL-17 inhibitor (secukinumab) were incubated with endothelial cells of healthy volunteers in an assay to measure ongoing inflammation. Patients on the TNF-αor IL-17 inhibitor demonstrated a level of leukocyte-endothelium interactions similar to those in healthy volunteers, whereas those treated with IL-12/23 inhibitors continued to demonstrate an inflammatory milieu. The same findings were demonstrated when applied to a psoriasis mouse model.

• These findings in vitro and in a mouse model support the results of recent clinical studies showing reduction of major adverse cardiac events by TNF-α inhibitors and secukinumab but not ustekinumab. These findings may help in choosing a biologic treatment for psoriasis patients with cardiovascular risk factors and support the early initiation of such treatment.

– Margaret Hammond, MD

Written by

 

 

Nicholas Brownstone MD

Written by

 

 

John Koo MD

Even though this study involved an animal model of psoriasis rather than observed effects on psoriatic plaques in humans, the findings are highly relevant to the clinical use of biologic agents. Using an imiquimod-induced psoriasis model in mice, the authors first established that the blood of psoriasis patients showed an increase in proinflammatory activity such as increased PMN migration and adhesion. This peaked with full development of the psoriatic lesions. Then the authors used anti-TNF, anti–IL-17, and anti–IL-12/23 biologic agents to see if the vascular inflammatory effects of the blood from psoriasis patients could be reversed or not. Most interestingly, they have found that adalimumab and secukinumab did, in fact, reverse inflammatory tendencies in the imiquimod-induced psoriasis model, but ustekinumab did not.

It has only been a decade since we have realized that psoriasis is more than a skin disease and involves serious comorbidities, such as increased risk of myocardial infraction, stroke, and sudden cardiac death. Obviously, a large-scale clinical trial is needed to validate these findings from this animal model of psoriasis. However, the results from this study further advance the understanding of these important comorbidities by suggesting that biologic agents may not be created equal with regard to their capacity for decreasing vascular inflammation in psoriasis patients. Moreover, the implications from these data may help clinicians choose among many biologic agents to optimize patient benefits not only with regard to the skin, but also for the entire body. For patients with psoriasis, treatment with select biologic agents early and continuously could prevent and possibly reverse vascular inflammation, atherosclerosis, and ultimately reduce cardiovascular morbidity and mortality.

Abstract 

The high prevalence of atherosclerosis in psoriatic patients is consistent with a chronic low-grade vascular inflammation (Puig, 2018), a symptom associated with a variety of cardiovascular (CV) events. The possibility that biological anti-inflammatory drugs used to treat the cutaneous manifestations of psoriasis also target this accompanying vascular inflammation raises their therapeutic potential. The present study addresses this issue by means of a comprehensive experimental protocol incorporating an <i>in vitro</i> functional approach using blood samples from psoriatic patients and a well-established translational animal model of the disease. Our aim was three-fold: a) to evaluate if psoriasis has any impact on leukocyte/endothelium interactions, a hallmark of vascular inflammation which represents an early stage of the atherosclerotic plaque formation and precedes the generation of thrombi; b) to explore the influence of several of the currently used biologics on such interactions; and c) to determine how psoriasis-associated vascular dysfunction impacts on thrombi formation - an end-stage event - and its modulation by biologics.

Journal of Investigative Dermatology

Differential Effects of Biologics on Psoriasis-Related Vascular Inflammation and Risk of Thrombosis

J Invest Dermatol 2020 Apr 17;[EPub Ahead of Print], P García-Martínez, V Collado-Díaz, A Mateu-Puchades, C Villarroel-Vicente, S Rovira-Llopis, A Blas-García, Á Álvarez, JV Esplugues, I Andújar

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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