In a recent 39-patient trial, week 12 reductions in aortic vascular inflammation (AVI) achieved by patients on ustekinumab did not persist through week 52. Nevertheless, it's the first biologic drug to show temporary impact on vascular inflammation, while reductions in some systemic markers of inflammation did last 52 weeks.
"In psoriasis, there is intense interest in understanding if therapies will lower cardiovascular risk over time. And there's interest in this phenomenon in cardiovascular medicine in general, because we know that many patients have heart attacks or strokes that are related to chronic inflammation, not necessarily to traditional cardiovascular risk factors,” says lead author Joel M. Gelfand, M.D., MSCE. “So, there is a need to identify therapies that can lower cardiovascular risk by lowering inflammation in blood vessels in a way that will reduce heart attacks and strokes."
Dr. Gelfand says it is clear from previous research that TNF inhibitors and secukinumab do not alter AVI versus placebo. In the Vascular Inflammation in Psoriasis (VIP)-U trial, however, 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) showed that at week 12, ustekinumab-treated patients had an 18.65% reduction in AVI versus placebo-treated patients (P = 0.001).
"But when we followed people for a total of 52 weeks on the drug, they were back to their baseline levels of aortic vascular inflammation,” he says.
Like the changes in AVI, statistically significant reductions in VCAM-1 that appeared at 12 weeks did not last until week 52. This protein mediates adhesion of lymphocytes to vascular endothelium and is believed to be important in atherosclerosis.
"Reducing VCAM-1 seems to suggest potential benefits in vascular health because essentially it would help limit the ability of immune cells to enter the vasculature and promote vascular disease," says Dr. Gelfand.
This study was funded by a grant to the University of Pennsylvania from Janssen Pharmaceuticals. Dr. Gelfand has served and received honoraria as a consultant for BMS, Boehringer Ingelheim, Janssen, Novartis, Sanofi, Pfizer and UCB. He has also received research grants (made to the University of Pennsylvania) from AbbVie, Boehringer Ingelheim, Celgene, Janssen, Novartis, Ortho Dermatologics and Pfizer.
1. Gelfand JM, Shin DB, Alavi A, et al. A phase IV, randomized, double-blind, placebo-controlled crossover study of the effects of ustekinumab on vascular inflammation in psoriasis (the VIP-U Trial). J Invest Dermatol. 2020;140:85-93.