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Circ Cardiovasc Imaging. 2017 Sep;10(9). pii: e006283. doi: 10.1161/CIRCIMAGING.117.006283.

Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.

Author information

1
From the Second Department of Cardiology (I.I., G.M., M.V., G.P., H.T., J.P., E.I., J.L.), Second Department of Dermatology and Venereology (E.P., K.T., D.R.), Department of Biological Chemistry (P.M., C.P.), and Department of Clinical Biochemistry (P.M., C.P.), Attikon Hospital, National and Kapodistrian University of Athens Medical School, Greece; and Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens School of Pharmacy, Greece (I.A., K.G.). ignoik@gmail.com.
2
From the Second Department of Cardiology (I.I., G.M., M.V., G.P., H.T., J.P., E.I., J.L.), Second Department of Dermatology and Venereology (E.P., K.T., D.R.), Department of Biological Chemistry (P.M., C.P.), and Department of Clinical Biochemistry (P.M., C.P.), Attikon Hospital, National and Kapodistrian University of Athens Medical School, Greece; and Department of Pharmaceutical Chemistry, National and Kapodistrian University of Athens School of Pharmacy, Greece (I.A., K.G.).

Abstract

BACKGROUND:

Interleukin (IL)-12 activity is involved in the pathogenesis of psoriasis and acute coronary syndromes. We investigated the effects of IL-12 inhibition on vascular and left ventricular (LV) function in psoriasis.

METHODS AND RESULTS:

One hundred fifty psoriasis patients were randomized to receive an anti-IL-12/23 (ustekinumab, n=50), anti-tumor necrosis factor-a (TNF-α; etanercept, n=50), or cyclosporine treatment (n=50). At baseline and 4 months post-treatment, we measured (1) LV global longitudinal strain, twisting, and percent difference between peak twisting and untwisting at mitral valve opening (%untwMVO) using speckle-tracking echocardiography, (2) coronary flow reserve, (3) pulse wave velocity and augmentation index, (4) circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), TNF-α, IL-6, IL-12, IL-17, malondialdehyde, and fetuin-a. Compared with baseline, all patients had improved global longitudinal strain (median values: -17.7% versus -19.5%), LV twisting (12.4° versus 14°), %untwMVO (27.8% versus 35%), and coronary flow reserve (2.8 versus 3.1) and reduced circulating NT-proBNP, IL-17, TNF-α, and IL-6 post-treatment (P<0.05). Compared with anti-TNF-α and cyclosporine, anti-IL-12/23 treatment resulted in a greater improvement of global longitudinal strain (25% versus 17% versus 6%,), LV twist (27% versus 17% versus 1%), %untwMVO (31% versus 27% versus 17%), and coronary flow reserve (14% versus 11% versus 4%), as well as a greater reduction of IL-12 (-25% versus -4% versus -2%), malondialdehyde (-27% versus +5% versus +26%), and NT-proBNP(-26% versus -13.6% versus 9.1%) and increase of fetuin-a (P<0.01). Pulse wave velocity and augmentation index were improved only after anti-IL-12/23 treatment and correlated with changes in global longitudinal strain, LV twisting-untwisting (P<0.05).

CONCLUSIONS:

In psoriasis, IL-12/23 inhibition results in a greater improvement of coronary, arterial, and myocardial function than TNF-α inhibition or cyclosporine treatment.

CLINICAL TRIAL REGISTRATION:

URL: http://www.clinicaltrials.gov. Unique identifier: NCT02144857.

KEYWORDS:

interleukin-12; psoriasis; pulse wave analysis; skin disease; ustekinumab

PMID:
28899951
DOI:
10.1161/CIRCIMAGING.117.006283
[Indexed for MEDLINE]

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