A Phase IV, Randomized, Double-Blind, Placebo-Controlled Crossover Study of the Effects of Ustekinumab on Vascular Inflammation in Psoriasis (the VIP-U trial).

Abstract

BACKGROUND\nPsoriasis is a Th17 autoimmune disease associated with an increased risk cardiovascular events and mortality. Ustekinumab, an antibody to p40, blocks cytokines IL12 and IL23, and is a highly effective and safe treatment for psoriasis.\n\n\nTRIAL DESIGN AND METHODS\nWe conducted a randomized double blinded placebo-controlled trial to determine the effect of ustekinumab on aortic vascular inflammation measured by imaging, and key biomarkers of inflammation, lipid and glucose metabolism in the blood of patients with moderate to severe psoriasis.\n\n\nRESULTS\n43 patients were randomized and at week 12, ustekinumab treated patients had an -18.65% (95% CI: -29.45% to -7.85%) reduction in aortic vascular inflammation at week 12, a reduction in inflammatory biomarkers, and an increase in apolipoprotein-B lipoproteins compared to placebo. At week 12, placebo patients crossed over such that all patients received ustekinumab for a total of 52 weeks. At the end of 52 weeks of ustekinumab treatment there was no change in aortic vascular inflammation compared to baseline, inflammatory markers were reduced and there were increases in selected measures of lipids and leptin.\n\n\nCONCLUSIONS\nThese results demonstrate blockade of IL12/23 may transiently reduce aortic vascular inflammation with more durable reduction in inflammatory cytokines associated with cardiovascular disease.