Ustekinumab reduces serum protein levels associated with cardiovascular risk in psoriasis vulgaris

Abstract

Psoriasis increases the risk of cardiovascular disease (CVD). Biomarkers for cardiovascular (CV) risk stratification in psoriasis are lacking, and the effects of psoriasis biologics on CV risk reduction remain unclear. The goal of this study was to identify biomarkers of CV risk in psoriasis blood that are reduced by ustekinumab. We quantified 276 inflammatory and CV‐related serum proteins with Olink's multiplex assay in 10 psoriasis patients (vs. 18 healthy controls) and after 12 weeks of ustekinumab treatment. For each protein down‐regulated after treatment, the literature was reviewed for studies assessing the protein's association with CVD. Data were collected from each study to calculate CV risk thresholds for each protein, which were compared with protein levels in psoriasis patients before and after treatment. Our results showed that 43 out of 276 proteins were down‐regulated after treatment, 25 of which were initially up‐regulated at baseline (vs. controls, all p‐values ≤0.1). 8 down‐regulated proteins were initially elevated above thresholds associated with enhanced CV risk in the literature (myeloperoxidase, C‐X‐C motif chemokine 10, E‐selectin, interleukin‐6, cystatin B, von Willebrand factor, tumor necrosis factor receptor 1 and N‐terminal prohormone brain natriuretic peptide). Treatment lowered these proteins to below their risk thresholds, except for IL‐6, which was lowered but remained at its risk threshold despite successful psoriasis skin treatment. In summary, 12 weeks of ustekinumab treatment reduced serum proteins present at levels associated with CV risk in psoriasis patients. Further studies can evaluate these proteins as potential ustekinumab‐modulated biomarkers of CV risk in psoriasis and the impact of ustekinumab on CV risk reduction.

Exposure–response relationship of guselkumab and the potential of serum proteomics in identifying predictive biomarker candidates in psoriasis

“…With our proteomics substudy, we intended to pave the way in discovering pharmacodynamic signatures capable of predicting GUS response. Despite using a sample size comparable to other Olink® studies [36][37][38][39][40] and that the Olink® assay was able to identify DEPs (e.g. between psoriasis patients and healthy controls), we could not identify predictive candidates with the chosen protein panel.…”

Administration Details of Genetically Engineered Biologic Drug (Ustekinumab) in Children with Psoriasis and Comorbid Metabolic Syndrome or in Case of Previous Biological Therapy Failure: Case Studies

“…В таких случаях назначение устекинумаба может быть более эффективным и предпочтительным -как за счет патогенетического воздействия на широкий спектр ключевых провоспалительных цитокинов, так и по причине невлияния на риск развития серьезных сердечно-сосудистых событий на фоне терапии [38,39]. В этой связи интересны результаты исследований, согласно которым блокада IL-12/IL-23 может кратковременно уменьшать воспаление аортальных сосудов с более стойким снижением продукции воспалительных цитокинов, связанных с сердечно-сосудистыми заболеваниями [22,40]. Кроме того, метаанализ последних исследований показал, что устекинумаб является более эффективным по сравнению с другими ГИБП и «классическими» иммуносупрессорами у пациентов с псориазом и сопутствующим ожирением [41].…”

Psoriasis and Molecular Target Therapies: Evidence of Efficacy in Preventing Cardiovascular Comorbidities

“…Initial studies seemed to show an increased risk of MACE associated with this drug but were soon disproved [ 40 ]. Contrarily, recent studies show that ustekinumab has a cardioprotective effect, as its use for 12 weeks reduces blood levels of several proteins elevated in psoriasis and associated with inflammation and cardiovascular risk, such as E-selectin, von Willebrand factor, IL-6 and myeloperoxidase [ 43 ]. Regarding adipokines, Onsun et al observed that during 48 weeks of therapy blood levels of leptin, adiponectin and omentin were significantly higher in ustekinumab-treated patients than in anti-TNF-treated patients, although these values correlated positively with response rates to therapy [ 44 ].…”