The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

Wcisło‐Dziadecka, Dominika; Grabarek, Beniamin Oskar; Kruszniewska‐Rajs, Celina; Strzałka‐Mrozik, Barbara

doi:10.1111/dth.12843

Cited by 6 publications

(5 citation statements)

References 5 publications

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“…The first treatment options for moderate-to-severe plaque psoriasis are the anti-TNF drugs ADA and ETN and the IL-12/23 inhibitor UTK [22,23]. Second-line treatments include the IL-17 inhibitors SCK and IXE and BDL targeting the IL-17RA receptor [24,25].…”

Section: Introductionmentioning

confidence: 99%

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

Jiménez

Ramírez

Martín

et al. 2021

JPM

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Psoriasis is a chronic inflammatory skin pathology of autoimmune origin and unknown etiology. There are various therapies for treating it, including a wide range of biopharmaceuticals indicated in moderate-to-severe psoriasis. Depending on their therapeutic target, they are classified as tumor necrosis factor inhibitors (anti-TNF) or cytokine inhibitors (interleukin-12, 23, and 17 antagonists). Although they have proved effective and safe, in clinical practice, many patients show a short- and long-term suboptimal response and even varying degrees of toxicity. This variability in response may be influenced by genetic factors, such as polymorphisms in the genes involved in the pathological environment, metabolism or mechanism of action of the drug that could affect the effectiveness and toxicity of biological therapies. This review assesses pharmacogenetic studies of the impact of genetic factors on response to biopharmaceuticals and toxicity in patients diagnosed with moderate-to-severe psoriasis. The results suggest that polymorphisms detected in the HLA genes, in genes that encode cytokines (TNF, IL genes, TNFAIP3), transporters (PDE3A-SLCO1C1, SLC12A8), receptors (TNFRSF1B, CD84, FCGR2A and FCGR3A, IL17RA, IL23R, TLR genes, PGLYRP4) and associated proteins (TNFAIP3, LY96, TIRAP, FBXL19), as well as other genes implicated in the pathogenesis of psoriasis (CDKAL1, CARD14, PTTG1, MAP3K1, ZNF816A, GBP6, CTNNA2, HTR2A, CTLA4, TAP1) can be used in the future as predictive markers of treatment response and/or toxicity with biological therapies in patients diagnosed with moderate-to-severe psoriasis, tailoring treatment to the individual patient.

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Section: Introductionmentioning

confidence: 99%

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

Jiménez

Ramírez

Martín

et al. 2021

JPM

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“…This indicates that anti‐IL12/23 therapy affects signaling induced by changes in the phosphorylation of JAK kinases and STAT proteins (Danese, Argollo, Le Berre, & Peyrin‐Biroulet, ; Soendergaard, Bergenheim, Bjerrum, & Nielsen, ). Nevertheless, taking into account our earlier molecular analysis carried out in the group of patients with psoriasis treated with ustekinumab (Wcisło‐Dziadecka, Grabarek, Kruszniewska‐Rajs, & Strzałka‐Mrozik, ) confirms the significant contribution of p19 subunit IL23 to the regulation of gene transcription activity, for example, IL17 (Cui et al, ). It seems that the predominance of STAT3 expression in comparison to STAT1 results from the promotion of IL23‐induced signaling (p19).…”

Section: Discussionmentioning

confidence: 73%

The influence of ustekinumab on expression of STAT1 , STAT3 , STAT4 , SOCS2 , and IL17 in patients with psoriasis and in a control

Grabarek

Krzaczyński

Strzałka‐Mrozik

et al. 2019

Dermatologic Therapy

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The aim of this study was to assess changes in the expression of STAT1, STAT3, STAT4, SOCS2, and IL17 in psoriatic patients under ustekinumab treatment and in healthy volunteers. The study group consisted of 14 patients suffering from psoriasis vulgaris qualified for ustekinumab therapy (4 women, 10 men) The control group consisted of 14 healthy volunteers (7 women, 7 men), their whole blood was used as a material in this study. A quantitative reverse transcription polymerase chain assay was used to amplify analyzed genes. To indicate the differences in expression of selected genes in the test and control groups, the Kruskal–Wallis and the post hoc Dunn's test was carried out. After 40 weeks of observation of the effectiveness of ustekinumab in patients with psoriasis, the expression of STAT1, STAT3, STAT4, IL17, and SOCS2 was silenced. Statistic differences in expression were observed for STAT3 (40 vs. 0 weeks, p < .05; 0 week vs. C, p < .05) and SOCS2 (0 week vs. C, p < .05). Patients with psoriasis vulgaris have higher levels of STAT1, STAT3, STAT4, SOCS2, and IL17 expression compared to healthy individuals. On the other hand, the treatment of ustekinumab lasting 40 weeks caused a decrease in the transcriptional activity of the analyzed genes.

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“…It is also worth mentioning that there are some biological drugs whose mechanism of action is associated with blocking p40 subunits. These include ustekinumaba human monoclonal antibody that binds to the p40 subunit of IL-12 and IL-23 cytokines, and thus blocks their interaction with the IL-12Rb1 receptor [25,26]. Due to its high repeatability and reproducibility, PASI is the most commonly used tool for measuring the severity of psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of molecular markers as IL-12, IL-22 and IFN-γ in correlation with a clinical course in patients with psoriasis

Kutwin

Migdalska-Sęk

Brzeziańska-Lasota

et al. 2020

Int J Occup Med Environ Health

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As a chronic, recurrent, immunologically mediated systemic disease and a common cause of dermatological problems, psoriasis is often a subject of scientific research. Skin changes located on the hands can cause difficulties and limitations in the performance of professional activities, especially manual ones. The main role in pathogenesis is played by immunological factors-improper functioning of the components of the immune system, among others, T lymphocytes and cytokines like interleukin-12 (IL-12), interleukin-22 (IL-22) and interferon gamma (IFN-γ). Material and Methods: The obtained tissue and blood were destined for RNA isolation. The RNA was then subjected to a reverse transcription reaction. The relative gene expression level was evaluated by the real-time polymerase chain reaction for IL-12B, IL-22 and IFN-γ genes, and presented as the relative quantification (RQ) value, relative to the reference gene GAPDH. In addition, a correlation analysis of the expression level of selected genes with the clinical course of the disease, as assessed by the Psoriasis Area and Severity Index (PASI), the Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI) scores was performed. Results: Statistical analysis confirmed a significant increase in RQ values for IL-12B, IL-22 and IFN-γ in the group of psoriatic patients vs. the control group. A positive correlation was also found between BSA and PASI and RQ for the IL-12B gene. Conclusions: Increased expression levels of IL-12B, IL-22 and IFN-γ genes in psoriatic skin confirm that selected cytokines play an important role in the initiation and sustenance of psoriasis.

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The analysis of the therapeutic potential of ustekinumab in psoriasis vulgaris treatment

Cited by 6 publications

References 5 publications

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

Influence of Genetic Polymorphisms on Response to Biologics in Moderate-to-Severe Psoriasis

The influence of ustekinumab on expression of STAT1 , STAT3 , STAT4 , SOCS2 , and IL17 in patients with psoriasis and in a control

Analysis of molecular markers as IL-12, IL-22 and IFN-γ in correlation with a clinical course in patients with psoriasis

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