Lowering Interleukin-12 Activity Improves Myocardial and Vascular Function Compared With Tumor Necrosis Factor-a Antagonism or Cyclosporine in Psoriasis.
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.
['Ikonomidis|Ignatios|I|', 'Papadavid|Evangelia|E|', 'Makavos|George|G|', 'Andreadou|Ioanna|I|', 'Varoudi|Maria|M|', 'Gravanis|Kostas|K|', 'Theodoropoulos|Kostas|K|', 'Pavlidis|George|G|', 'Triantafyllidi|Helen|H|', 'Moutsatsou|Paraskevi|P|', 'Panagiotou|Christina|C|', 'Parissis|John|J|', 'Iliodromitis|Efstathios|E|', 'Lekakis|John|J|', 'Rigopoulos|Dimitrios|D|']
D000328:Adult D001696:Biomechanical Phenomena D003326:Coronary Circulation D016572:Cyclosporine D018618:Echocardiography, Doppler, Color D018619:Echocardiography, Doppler, Pulsed D000068800:Etanercept D005260:Female D006115:Greece D006801:Humans D007166:Immunosuppressive Agents D018664:Interleukin-12 D008297:Male D008875:Middle Aged D009200:Myocardial Contraction D020097:Natriuretic Peptide, Brain D018384:Oxidative Stress D010446:Peptide Fragments D011565:Psoriasis D063177:Pulse Wave Analysis D020127:Recovery of Function D013997:Time Factors D016896:Treatment Outcome D014409:Tumor Necrosis Factor-alpha D000069549:Ustekinumab D059289:Vascular Stiffness D016277:Ventricular Function, Left D060749:alpha-2-HS-Glycoprotein
interleukin-12 psoriasis ustekinumab pulse wave analysis skin disease