Blockage of IL-12/23 May Transiently Reduce Aortic Vascular Inflammation in Patients With Psoriasis

Interleukin 23
Interleukin 23
Antibody-based therapies such as ustekinumab can causally decrease aortic vascular inflammation.

Aortic vascular inflammation in patients with moderate to acute psoriasis may be transiently reduced by blocking interleukin (IL)-12 and IL-23, according to a study in the Journal of Investigative Dermatology. This blockage may reduce inflammatory cytokines for more sustained periods.

This randomized, placebo-controlled, double-blind trial included 43 participants (average age, 42±13.38; 70% men) randomly assigned to either ustekinumab (n=22) or placebo (n=21). Those in the intervention group completed 12 weeks of the study compared with 86% (n=19) of the placebo group. The placebo group was switched to ustekinumab at week 12 so that all participants were treated with ustekinumab for a year. To investigate the response of aortic vascular inflammation to ustekinumab, 18F-2-fluorodeoxyglucose-positron emission tomography/computed tomography imaging and examination of biomarkers were used, as were blood glucose and lipid metabolism. Change in total vascular inflammation constituted the primary outcome. Wilcoxon rank-sum tests and linear regressions were used to evaluate changes in biomarker and maximum target to background ratio values.

Compared with placebo, those treated with ustekinumab showed a relative decrease in aortic vascular inflammation of -18.65% (95% CI, -29.45 to -7.85), as well as an increase in apolipoprotein-B lipoproteins and a decrease in blood inflammatory biomarkers. At week 12 compared with baseline, the changes in aortic vascular inflammation for the ustekinumab vs placebo groups were -6.58% (95% CI, -13.64 to 0.47) and 12.07% (95% CI, 3.26-20.88), respectively. By the end of the year-long ustekinumab treatment, aortic vascular inflammation showed no change from baseline (0.84% change; 95% CI, -4.38 to 6.07), though certain measurements of lipids and leptin increased and inflammatory markers decreased.

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Limitations to this study included having a small sample size, inherent limitations of positron emission tomography imaging, the inability of aortic vascular inflammation to directly measure coronary disease, and an inability to evaluate whether IL-12/23 blockage mediated targeting. 

Study researchers concluded that “IL-12/23 may transiently reduce aortic vascular inflammation (ie, improvements seen at week 12, no difference at 12 months) with more durable reduction in inflammatory cytokines associated with cardiovascular disease. It is important to emphasize that we evaluated blood and imaging biomarkers of cardiovascular events, and thus, ultimately large-scale, long-term, event-driven trials will be necessary to determine the clinical benefits of treatments for psoriasis on cardiovascular disease.”

Disclosure: This clinical trial was supported by Janssen Pharmaceuticals. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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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) [published online July 18, 2019]. J Invest Dermatol. doi: 10.1016/j.jid.2019.07.679