Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose PET/CT

Kim, Byung Soo; Lee, Won‐Ku; Pak, Kyoungjune; Han, Junhee; Kim, Gun‐Wook; Kim, Hoon-Soo; Ko, Hyun‐Chang; Kim, Moon‐Bum; Kim, Seong-Jang

doi:10.1016/j.jaad.2018.03.011

Cited by 43 publications

(36 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At week 12, there was a significant (i.e., similar to statin effects) 18.65% decrease in AVI in patients treated with ustekinumab compared with placebo (Tawakol et al, 2013). This finding is proof of principle that antibody-based therapies can causally decrease AVI, and advances observations from prior uncontrolled studies, which showed an improvement in AVI in Korean patients with psoriasis treated with ustekinumab (Kim et al, 2019). Moreover, this finding appears specific to the IL-12 and IL-23 pathway, as similar trials by our group and others have shown a neutral effect of biologics that target TNF (adalimumab) and IL-17 (secukinumab), respectively (Bissonnette et al, 2017;Gelfand et al, 2019;Mehta et al, 2018).…”

Section: Discussionsupporting

confidence: 85%

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

Gelfand

Shin

Alavi

et al. 2020

Journal of Investigative Dermatology

100

View full text Add to dashboard Cite

Psoriasis is a T helper type 17 autoimmune disease associated with an increased risk cardiovascular events and mortality. Ustekinumab, an antibody to p40, blocks cytokines IL-12 and IL-23, and is a highly effective and safe treatment for psoriasis. We conducted a randomized double-blinded placebo-controlled trial to determine the effect of ustekinumab on aortic vascular inflammation (AVI) measured by imaging, and key biomarkers of inflammation, lipid, and glucose metabolism in the blood of patients with moderate-to-severe psoriasis. A total of 43 patients were randomized, and at week 12, ustekinumab-treated patients had a e18.65% (95% confidence interval ¼ e29.45% to e7.85%) reduction in AVI, a reduction in inflammatory biomarkers, and an increase in apolipoprotein B lipoproteins compared with placebo. At week 12, placebo patients were crossed over such that all patients received ustekinumab for 52 weeks. At the end of 52 weeks of ustekinumab treatment, there was no change in AVI compared with baseline, inflammatory markers were reduced, and there were increases in selected measures of lipids and leptin. These results show that blockade of IL-12 and/or IL-23 may transiently reduce AVI, with more durable reduction in inflammatory cytokines associated with cardiovascular disease.

show abstract

Section: Discussionsupporting

confidence: 85%

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

Gelfand

Shin

Alavi

et al. 2020

Journal of Investigative Dermatology

100

View full text Add to dashboard Cite

show abstract

“…However, one of these studies evaluated several biomarkers and found decreased levels of glycoprotein acetylation, a novel composite biomarker of systemic inflammation, in patients treated with adalimumab compared with those treated with phototherapy . Additionally, a small prospective study of ustekinumab in a Korean population observed significantly decreased vascular inflammation in individuals who achieved ≥ 75% improvement in PASI over a mean treatment period of 5 months . Ongoing prospective studies include Vascular Inflammation in Psoriasis (VIP) trials that are currently evaluating the effects of ustekinumab (VIP‐U; NCT02187172), secukinumab (VIP‐S; NCT02690701) and apremilast (VIP‐A; NCT03082729) on aortic inflammation as measured by 18 F‐FDG PET/CT and on levels of biomarkers associated with metabolic and cardiovascular risk.…”

Section: Goals For Treating Systemic Inflammation In Psoriasismentioning

confidence: 99%

“…57 Additionally, a small prospective study of ustekinumab in a Korean population observed significantly decreased vascular inflammation in individuals who achieved ≥ 75% improvement in PASI over a mean treatment period of 5 months. 58 Ongoing prospective studies include Vascular Inflammation in Psoriasis (VIP) trials that are currently evaluating the effects of ustekinumab (VIP-U; NCT02187172), secukinumab (VIP-S; NCT02690701) and apremilast (VIP-A; NCT03082729) on aortic inflammation as measured by 18 F-FDG PET/CT and on levels of biomarkers associated with metabolic and cardiovascular risk. Results from studies of biological agents in IMIDs other than psoriasis support the hypothesis that biological agents can reduce systemic inflammation and prevent cardiovascular damage.…”

Section: Goal 1: Prevent Damage Associated With Inflammation and Prevmentioning

confidence: 99%

Management of psoriasis as a systemic disease: what is the evidence?

2019

View full text Add to dashboard Cite

Summary Background Psoriasis is a chronic, systemic immune‐mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population. Objectives To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate‐to‐severe psoriasis. Methods This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis. Results Current evidence suggests that preventing damage associated with inflammation, and preventing development of future inflammatory damage and comorbidities, may be a potentially achievable treatment goal for many patients with moderate‐to‐severe plaque psoriasis when biological therapies are utilized early in the disease. Encouraging data from recent studies suggest that the loftier goal of reversing existing inflammatory damage and improving signs and symptoms of inflammatory comorbidities could also possibly be attainable. Conclusions Results from ongoing prospective studies regarding the effects of biologics on markers of systemic inflammation in patients with psoriasis will strengthen the clinical evidence base that can be used to inform treatment decisions for patients with moderate‐to‐severe psoriasis. What's already known about this topic? Psoriasis is a systemic inflammatory disease and treatments are needed to optimize patient outcomes. What does this study add? This review discusses new psoriasis treatment paradigms that may potentially reduce effects of systemic inflammation. Evidence demonstrating that biological treatment may prevent or reverse inflammatory damage associated with psoriasis comorbidities is reviewed.

show abstract

“…Для препарата характерны низкая иммуногенность и достаточно благоприятный профиль безопасности. По данным международных регистров, устекинумаб характеризуется самым высоким показателем «выживаемости» терапии среди всех ГИБП [39,41]. До настоящего времени не было проведено прямых сравнительных клинических испытаний между устекинумабом и другими препаратами, одобренными для лечения болезни Крона (инфликсимабом, адалимумабом, цертолизумаба пэголом или ведолизумабом).…”

Section: целесообразность раннего назначения генноинженерных препаратовunclassified

Psoriasis and inflammatory bowel diseases: pathogenetic pathways and the choice of biologic therapy (a literature review)

et al. 2019

View full text Add to dashboard Cite

Psoriasis and inflammatory bowel disease (IBD) are multifactorial chronic immuno-inflammatory potentially disabling disorders with similar genetic factors and immunological pathways, in particular, genetic polymorphisms of IL-23R, which determines the signal IL-12/23-mediated pathway of immunopathogenesis. The emergence of genetically engineered biological agents has changed the prognosis for both psoriasis and IBD. The intersection of the therapeutic spectrum in psoriasis and IBD is a very important point when choosing the management strategy for these patients. Infliximab and adalimumab are effective in the treatment of psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis (evidence level 1A). Ustekinumab demonstrates effectiveness in the treatment of psoriasis, psoriatic arthritis (evidence level 1A) and Crohn's disease (evidence level 1B). Etanercept and secukinumab have been shown to be effective against psoriasis, psoriatic arthritis (evidence level 1A) and ineffective and even associated with exacerbation risk in Crohn's disease and ulcerative colitis. Inhibition of regulatory cytokines IL-12/23 also has a number of advantages compared to the blockade of effector cytokines (TNF-α, IL-17) due to potentially long-term and stable treatment results and less frequent administration.

show abstract

Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose PET/CT

Abstract: Ustekinumab treatment was significantly associated with decreased systemic and vascular inflammation related to metabolic syndrome and cardiovascular disease among patients with psoriasis.

Cited by 43 publications

References 23 publications

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

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

Management of psoriasis as a systemic disease: what is the evidence?

Psoriasis and inflammatory bowel diseases: pathogenetic pathways and the choice of biologic therapy (a literature review)

Contact Info

Product

Resources

About