Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis - PubMed (original) (raw)

Randomized Controlled Trial

. 2017 Sep;10(9):e006283.

doi: 10.1161/CIRCIMAGING.117.006283.

Evangelia Papadavid 2, George Makavos 2, Ioanna Andreadou 2, Maria Varoudi 2, Kostas Gravanis 2, Kostas Theodoropoulos 2, George Pavlidis 2, Helen Triantafyllidi 2, Paraskevi Moutsatsou 2, Christina Panagiotou 2, John Parissis 2, Efstathios Iliodromitis 2, John Lekakis 2, Dimitrios Rigopoulos 2

Affiliations

Randomized Controlled Trial

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

Ignatios Ikonomidis et al. Circ Cardiovasc Imaging. 2017 Sep.

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.

© 2017 American Heart Association, Inc.

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