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

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.