Analysis of the clinical response and changes in the expression of TNF-α and its TNFR1 and TNFR2 receptors in patients with psoriasis vulgaris treated with ustekinumab

Wcisło‐Dziadecka, Dominika; Grabarek, Beniamin Oskar; Kruszniewska‐Rajs, Celina; Gola, Joanna; Simka, Klaudia; Mazurek, Urszula

doi:10.17219/acem/112607

Cited by 5 publications

(6 citation statements)

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“…In addition, the response to treatment in the present study shows nonsignificant difference in the distribution of different genotypes of TNFSFR1B (rs1061622) polymorphism between responders and non-responders patients. This result is in disagreement with (26) Vassilopoulos et al Who found that TT homozygosis is associated with a positive response, while Dirk Koczan et al(27) found that SNP rs1061622 on the TNFR1B gene is associated with a poorer response to anti-TNF therapy, as well as current work showed a highly significant difference between overall patients and controls regarding TNFRSF1B serum level this was similar to Dominika Ligia Wcisło-Dziadeckaet al(28) who found over expression of TNFRSF1B in the group of patients when compared to the control. Mayte Sua´rez-Farin˜aset al(29) was found increased expression of TNFRSF1B, as detected by serum and gene microarray assessments, in psoriasis patients.…”

contrasting

confidence: 78%

Impact of TNF-α and TNFR1B genes polymorphisms on disease susceptibility and predict response to anti-TNF therapy in psoriatic patients

Hadi¹,

Abbas²,

Abdulamir³

et al. 2020

ATMPH

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Background: Polymorphisms of genes including tumor necrosis factor alpha (TNF-α) and Tumor necrosis factor receptor super family 1B (TNFRSF1B) may influence susceptibility to psoriasis as well as patients' biological responses. Aim of the study: To demonstrate the potential roles of TNF-α and TNFR1B, genes polymorphism {TNF-α -308 (G/A) and TNFR1B rs1061622 (T/C)} in susceptibility to psoriasis, elucidating their possible influence on patients' biological drug response and serum level. Subjects and methods: One hundred psoriatic patients and 100 apparently healthy individuals as a controls were included in this study. Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) was performed to evaluate different TNF-α and TNFR1B genes polymorphism. TNF-α and TNFR1B serum levels were assessed by enzyme linked immune sorbent assay. Results: Comparison between overall patients and controls revealed a higher serum level of TNF-α in patients than the controls with a highly significant difference (P<0.001). The risk of psoriasis was observed among people who had TNF-α-308 AA or GA genotypes, namely A allele-containing genotypes. Regarding the response to treatment it was revealed that the mutant homozygous genotype AA with higher frequency in non-responder (85.7%). The risk of non-response to biological drug was higher in people carrying AA genotype than in people carrying GG or GA genotypes. Concerning to serum level of tumor necrosis factor receptor super family member 1B (TNFRSF1B), Present study showed a highly significant difference between overall patients and controls. TNFSFR1B (rs1061622) SNP, CC and CT genotypes were dominant in controls and psoriatic patients, whereas the mutant TT genotype was dominant only in psoriatic patients. High risk of psoriasis in subjects had TT genotype than subjects carrying CC genotype. The response to treatment in the present study shows non-significant difference in the distribution of different genotypes of TNFSFR1B (rs1061622) polymorphism between responders and non-responders patients. Conclusion: These results may provide an additional evidence for association of TNF-α -308G/A and TNFRSF1B rs1061622, genes polymorphism to psoriasis susceptibility and disease severity and may serve as predictive and prognostic biomarkers.

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contrasting

confidence: 78%

Impact of TNF-α and TNFR1B genes polymorphisms on disease susceptibility and predict response to anti-TNF therapy in psoriatic patients

Hadi¹,

Abbas²,

Abdulamir³

et al. 2020

ATMPH

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“…However, De Keyser et al ( 19 ) study and Van Vugt et al ( 24 ) meta-analysis conclude that there is no justification for excluding patients with negative HLA-C*06 for ustekinumab treatment. Analyzing the expression patterns of the TGF-β gene and transcription activity profiles of TNF-α, TNFR1, and TNFR2 may also be useful for monitoring ustekinumab therapy ( 25 , 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, there are several scales to assess effectiveness: PASI, Dermatology Life Quality Index (DLQI) and Body Surface Area (BSA) ( 26 , 27 ). In our study, only absolute PASI value was used, because it is the most useful criteria to assess whether the patient is within the therapeutic response parameters at any time ( 1 , 10 ).…”

Section: Discussionmentioning

confidence: 99%

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

et al. 2022

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IntroductionThere is growing evidence that therapeutic drug monitoring of biologic therapy is beneficial in psoriatic patients. With respect to ustekinumab, the available evidence has not shown any relationship yet. The objective of this study is to identify correlations among ustekinumab trough concentrations, anti-ustekinumab antibodies and clinical response in moderate-to-severe plaque psoriasis patients, in a real-world setting.MethodsObservational prospective follow-up study in psoriatic patients treated with ustekinumab. Patients were classified in optimal (PASI ≤ 3) and suboptimal responders (PASI > 3). Mann–Whitney U test and Spearman’s rank correlation coefficient were used. Receiver-operator characteristic curve analysis was performed to identify ustekinumab concentration cut-off to achieve optimal response. A p-value < 0.05 was considered statistically significant.ResultsA total of 59 patients were included. Forty-eight patients (81.4%) corresponded to optimal responders and 11 (18.6%) to suboptimal responders. There was significant difference to ustekinumab concentrations: 0.7 μg/mL (range <0.1–1.8) vs. 0.4 μg/mL (range <0.1–0.8) respectively (p = 0.007). Positive correlation between ustekinumab concentration and psoriasis area and severity index (PASI) value was detected (p = 0.009). A cut-off value of 0.6 μg/mL ustekinumab concentration was found to achieve clinical response. Anti-ustekinumab antibodies were detected in 2 (3.4%) samples, both suboptimal responders.ConclusionA positive correlation exits between ustekinumab concentration and clinical response (optimal response PASI values ≤ 3) in blood draws performed before drug administration. The measurement of anti-ustekinumab antibodies could be considered in treatment failure.

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“…117 However, it has also been shown that PsA patients receiving anti-TNF have better outcomes than anti-IL17/IL12/23 agents. 118 While considerable clinical efficacy of ustekinumab was seen in the trial by Wcislo-Dziadecka et al, 113 a concurrent rise in TNF-α and its receptors TNFR1 and TNFR2 suggested that the signaling pathway for TNF-α secretion may be engaged during therapy. Furthermore, bispecific antibodies that target both IL-12 p40 and TNF-α have been demonstrated to have a blocking effect on the onset of psoriasis in mice.…”

Section: Il-12 Familymentioning

confidence: 99%

“…Psoriasis patients on ustekinumab experienced a progressive decline in their PASI, body surface area (BSA), and DLQI scores. 113 It also inhibits PsA synovial inflammation by regulating multiple signaling pathways. 114 The risks associated with psoriatic comorbidities have gradually come to light in recent years, and anti-IL-12/23 therapy’s effectiveness in treating psoriatic comorbidities such as atherosclerosis and IBD has been confirmed.…”

Section: Il-12 Familymentioning

confidence: 99%

Interleukins and Psoriasis

Zhu,

Zhao,

Ding

et al. 2024

J Cutan Med Surg

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Psoriasis is an immune-mediated chronic inflammatory skin disease that affects 2% to 3% of the world’s population. It is widely assumed that immune cells and cytokines acting together play a crucial part in the pathophysiology of psoriasis by promoting the excessive proliferation of skin keratinocytes and inflammatory infiltration. Interleukins (ILs), as a critical component of cytokines, have been closely associated with the pathogenesis and progression of psoriasis. This review summarizes the current contribution of ILs to psoriasis and describes the role each IL performs in psoriasis. Furthermore, the paper presents the therapeutic effects and application prospects of biologics developed for ILs in clinical treatment and experiments. The study aims to further the research on ILs in the treatment of psoriasis.

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Analysis of the clinical response and changes in the expression of TNF-α and its TNFR1 and TNFR2 receptors in patients with psoriasis vulgaris treated with ustekinumab

Cited by 5 publications

References 0 publications

Impact of TNF-α and TNFR1B genes polymorphisms on disease susceptibility and predict response to anti-TNF therapy in psoriatic patients

Impact of TNF-α and TNFR1B genes polymorphisms on disease susceptibility and predict response to anti-TNF therapy in psoriatic patients

Real-world use of ustekinumab therapeutic drug monitoring in moderate to severe psoriasis

Interleukins and Psoriasis

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