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Studien
Plaque psoriasis frequently involves high-impact anatomical sites such as the scalp, nails, and palmoplantar regions, which are associated with significant functional impairment and reduced quality of life. Evidence on the long-term effectiveness of biologic therapies in these locations in real-world settings remains limited. This study aimed to evaluate the real-world effectiveness and safety outcomes of risankizumab in achieving complete clearance of psoriasis affecting high-impact sites over a 2-year period.Methods
We conducted a retrospective multicenter cohort study including adult patients with plaque psoriasis who initiated risankizumab between January 2020 and December 2023 across six dermatology centers. Effectiveness was assessed as the proportion of patients achieving complete clearance (Physician Global Assessment score of 0) in scalp, nail, and palmoplantar psoriasis.Results
Among 459 patients treated with risankizumab, 232 (50.5%) had involvement of at least one high-impact site at baseline. Complete clearance at 2 years was achieved in 72.5% of patients with scalp involvement, 64.7% of those with nail psoriasis, and 52.2% of those with palmoplantar disease. Adverse events were infrequent and not treatment-limiting.Conclusions
These findings support the effectiveness of risankizumab in high-impact psoriasis sites in real-world clinical practice.Weiterlesen
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Obesity contributes to inflammation and may decrease psoriasis treatment efficacy. We investigated whether obesity affects the efficacy and safety of tildrakizumab, an anti-interleukin-23 p19 antibody approved for the treatment of adults with moderate-to-severe plaque psoriasis, for scalp psoriasis treatment.Methods
This was a subgroup analysis of a randomized, double-blind, placebo-controlled, Phase 3b trial in patients with moderate-to-severe plaque psoriasis affecting the scalp. Patients receiving tildrakizumab 100 mg or placebo were analyzed by baseline obesity status (body mass index ≥ 30 versus < 30 kg/m2). Efficacy outcomes included an Investigator Global Assessment (IGA) modified 2011 (scalp) (IGA mod 2011 [scalp]) score of "clear"/"almost clear" (0/1) with a ≥ 2-point reduction (IGA mod 2011 [scalp] response), ≥ 90% improvement in Psoriasis Scalp Severity Index (PSSI) score (PSSI 90 response), ≥ 4-point reduction in Scalp Itch-Numeric Rating Scale (Scalp Itch-NRS response; among patients scoring ≥ 4 at baseline), and percent change from baseline (%CFB) in affected scalp surface area (SSA). Safety was assessed from adverse events. The analysis was not prospectively powered to detect differences between subgroups.Results
In the intention-to-treat population, 56/117 (47.9%) patients randomized to tildrakizumab and 57/114 (50.0%) to placebo had obesity (modified intention-to-treat population: tildrakizumab, 43/89 [48.3%]; placebo, 40/82 [48.8%]). At Week 16, significantly more patients treated with tildrakizumab versus those receiving placebo achieved IGA mod 2011 (scalp) (obesity, 21/43 [48.8%] versus 4/40 [10.0%], p = 0.0002; no obesity, 23/46 [50.0%] versus 2/42 [4.8%], p < 0.0001) and PSSI 90 responses (obesity, 27/43 [62.8%] versus 4/40 [10.0%], p < 0.0001; no obesity, 27/46 [58.7%] versus 0/42 [0.0%], p < 0.0001). Treatment effect was also maintained for Scalp Itch-NRS response (p < 0.0001) and mean %CFB in affected SSA (no statistical testing), regardless of obesity status. Results in patients treated with tildrakizumab were similar through Week 52. No new safety signals were identified.Conclusions
No statistically significant differences in efficacy or safety were observed between patients with and without obesity.Clinicaltrials
Gov identifier
NCT03897088.Weiterlesen
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Patients with psoriasis (PsO) are at increased risk of developing psoriatic arthritis (PsA). Emerging evidence suggests that biologic therapies may differentially influence the development of PsA; however, there are no data on the relative ability of second-line biological therapy to prevent PsA.Aim
To evaluate the impact of biologic therapy on the risk of incident PsA in patients with PsO with a focus on second-line biologic therapy.Methods
We identified 2819 patients who initiated biologic therapy for PsO between 2002 and 2022, including Tumor Necrosis Factor (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-23p19 inhibitors and IL-12/23 inhibitors. The primary outcome was incident PsA. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate arthritis-free survival and HRs for the development of PsA. Risk was assessed separately for first-line and second-line biologic therapy.Results
Among 2819 patients with PsO initiating first-line biologic therapy, 400 (14.2%) developed PsA. In multivariable Cox regression, first-line anti-IL-23p19 agents were significantly associated with a lower risk of developing PsA compared with TNF inhibitors (HR 0.13; 95% CI 0.02 to 0.96; p=0.045). Among 1246 patients receiving second-line biologics, 125 (10.0%) developed PsA. Notably, in second-line therapy, only IL-17 inhibitors were independently associated with a statistically significant reduction in PsA risk versus TNF inhibitors (HR 0.37; 95% CI 0.16 to 0.85; p=0.019), with trends observed for anti-IL-12/23 (HR 0.14; 95% CI 0.02 to 1.05; p=0.056) and anti-IL-23p19 (HR 0.46; 95% CI 0.20 to 1.07; p=0.070).Conclusions
This is the first study to evaluate second-line biological therapy in relation to PsA risk. IL-17 inhibitor therapy was significantly associated with a reduced risk of incident PsA compared with TNF inhibitors.Weiterlesen
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Linear psoriasis is a rare variant of psoriasis characterized by erythema and scaling along the Blaschko lines. Its pathogenesis remains unknown.Objective
To investigate the molecular and immunological mechanisms of linear psoriasis through gene mutation analysis and in vitro experiments and identify potential combined therapeutic targets for psoriasis.Methods
Whole-exome sequencing was performed on linear lesion, clinically normal skin, and peripheral blood from linear psoriasis patient to identify somatic mutations. Candidate gene expression was assessed using public RNA-seq data of linear and classic psoriasis vulgaris, dataset before and after IL-17 antagonist Brodalumab treatment, and single-cell data of recurrent psoriasis lesions. Immunofluorescence staining confirmed gene expression and distribution. In vitro keratinocyte assays evaluated effects on proliferation and inflammation. Based on these findings, the patient received IL-17 antagonist therapy (Ixekizumab).Results
An increased copy number variant of Glycosyltransferase 1 Domain Containing 1 (GLT1D1), not previously reported, was identified in the epidermis of linear psoriasis. GLT1D1 was highly expressed in both linear psoriasis and classic psoriasis vulgaris, as well as in recurrent lesions and in patients who failed to achieve PASI75 with IL-17 antagonist therapy. In keratinocytes, GLT1D1 overexpression promoted cell proliferation, enhanced proinflammatory cytokine secretion, and activated IL-17 signaling, particularly via IL-17RE upregulation. In imiquimod-induced mouse models, GLT1D1 overexpression aggravated psoriasiform inflammation. Clinical improvement was observed in the patient after treatment with ixekizumab.Conclusion
GLT1D1, with an abnormally high copy number, may contribute to psoriasiform changes in keratinocytes by promoting proliferation, increasing proinflammatory cytokine secretion, and enhancing IL-17RE expression.Weiterlesen
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To quantify sociodemographic differences in the prevalence of diagnosed psoriasis and to evaluate temporal trends in its epidemiologic distribution.Methods
Data from the 2003-2006 and 2009-2014 National Health and Nutrition Examination Survey and the 2023-2024 National Health Interview Survey were analyzed. Meta-analysis was performed to determine whether age, sex, race/ethnicity, interview language, marital status, BMI, education, income, and health insurance are independently associated with odds of diagnosed psoriasis. Estimates from each survey period were tested for linear trends over time.Results
The total sample included 53,225 participants. Spanish speakers, compared to English speakers, demonstrated markedly lower prevalence of diagnosed psoriasis (pooled aOR = 0.40, 95% CI = 0.25-0.65), even after adjusting for other sociodemographic factors including race/ethnicity. Other factors independently associated with psoriasis were older age, non-Hispanic White race/ethnicity, and higher BMI (all P < 0.001). No temporal trends in prevalence were found in any sociodemographic subgroup.Conclusion
This analysis of national data covering an almost 25-year period indicates psoriasis has consistently been one of the most common inflammatory skin diseases with a stable sociodemographic distribution over this time. High rates of potentially undiagnosed psoriasis among vulnerable sociodemographic subgroups may be a persistent issue spanning over 2 decades. Patients with limited English proficiency may have difficulty interacting with the healthcare system, leading to undiagnosed psoriasis. Difficulty of diagnosis in patients with skin of color may also contribute. Given that psoriasis is a condition with systemic effects, including impacts on cardiovascular risk, accurate and timely diagnosis is essential to ensure appropriate clinical management.Weiterlesen
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The online version contains supplementary material available at 10.1007/s10616-026-00969-x.Weiterlesen
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The aim of this study is to describe characteristics of children with the International League of Associations for Rheumatology (ILAR)-defined juvenile idiopathic arthritis (JPsA) and to assess whether more sensitive and specific criteria for defining JPsA can be identified.Methods
A retrospective observational multicentre study was conducted including patients with a diagnosis of JPsA according to ILAR criteria. In this population, we identified clusters using as variables the clinical criteria of JPsA according to ILAR and the CASPAR clinical criteria. In addition, we defined as undifferentiated arthritis patients that met the ERA criteria, as defined by ILAR, and presented psoriatic features such as psoriasis or a history of psoriasis or psoriatic arthritis in a first-degree relative.Results
73 patients were enrolled. Three clinical clusters were found using unsupervised principal component analysis for the patients. Cluster 1 differed significantly for older patients and psoriasis. In contrast, Cluster 2 was mainly characterised by dactylitis and Cluster 3 was defined by family history of psoriasis and a significant prevalence of dactylitis. We also showed a statistically significant presence of familiarity for psoriatic arthritis in Cluster 2. The significance for all parameters evaluated did not change even when we included the patients with undifferentiated arthritis, except for MTX treatment, which was significantly more common in Cluster 2 (p=0.02), and tenosynovitis, also in Cluster 2 (p=0.05). Moreover, we evaluated our cohort by the Vancouver criteria. Combining the ILAR, CASPAR, and Vancouver criteria only two patients remain undifferentiated.Conclusions
Our study showed three clinical clusters with diverse demographic and clinical characteristics, indicating JPsA heterogeneity. The findings highlight the need to look beyond ILAR criteria for clinical variables, including family history of psoriatic arthritis. The ILAR, CASPAR, and Vancouver criteria improve the diagnosis of paediatric psoriatic spectrum arthritis. This complex disease population needs larger cohorts and clinical data, especially on axial involvement, to better categorisation and treatment.Weiterlesen
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Psoriasis is an immune-mediated inflammatory skin condition that is chronic and causes a great deal of disease burden, especially for those affected in their most productive years. Gut microbiota, immune parameters and, in turn, psoriasis symptom improvement have recently been associated with the use of probiotics in several different studies.Objectives
This study aims to conduct an umbrella review of systematic reviews and meta-analyses of the effectiveness of probiotic supplementation as a possible adjuvant in the treatment of psoriasis.Methods
This umbrella review is listed in the PROSPERO database (registration number CRD420251130518) and was referenced according to the PRISMA 2020 guidelines. The data were obtained after a systematic search of the literature in Cochrane, Scopus and PubMed. The quality of the methodology was evaluated using the AMSTAR 2 tool; the overlap was evaluated with the corrected covered area (CCA) method.Discussions
Five systematic reviews and meta-analyses were included, covering hundreds of adult psoriasis patients. The probiotics studied consisted of both single-strain and multistrain formulations, sometimes combined with prebiotics. Probiotics are associated with significantly reduced Psoriasis Area and Severity Index (PASI) scores, increased PASI 75 response rates, lowered inflammatory biomarkers (CRP, TNFα, IL-6) and improved Dermatology Life Quality Index (DLQI). Greater effectiveness was found with multistrain probiotics, treatment duration of ≥ 12 weeks and studies conducted in Asia. Most studies reported good safety and minimal side effects. However, a high overlap among included reviews was observed (CCA = 38.64%), which should be considered when interpreting the findings and their limitations.Conclusions
Probiotics, particularly multistrain formulations, show potential as a safe and effective adjuvant therapy for reducing psoriasis severity and improving patient quality of life. Further clinical trials are needed to identify the most effective strains and optimal duration of treatment.Weiterlesen
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Psoriasis is a chronic immune-mediated inflammatory disorder affecting both adults and children worldwide, with an average prevalence of approximately 2%. Recent evidence suggests that several hematological inflammatory parameters and vitamin levels may serve as accessible biomarkers for disease activity and severity assessment.Methods
This single-center retrospective case-control study was conducted at Jordan University Hospital using electronic medical record data from January 2019 to December 2023. The study included 142 patients with psoriasis and 277 age- and sex-matched controls. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI). Hematological inflammatory indices-including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)-as well as vitamin D and vitamin B12 levels were evaluated.Results
The mean age ± standard deviation was 43.76 ± 16.78 years, with no significant differences between psoriasis cases and controls. Females accounted for 54.93% of psoriasis cases compared with 54.41% of controls. The mean PASI score was 9.02 ± 9.00. Approximately 51.79% of psoriasis patients were vitamin D deficient, while 17.82% had vitamin B12 deficiency. No significant differences in psoriasis severity categories were observed across vitamin B12 or vitamin D levels (p = 0.808 and p = 0.184, respectively). The mean NLR, PLR, and SII were 2.21, 124.6, and 588,441.8, respectively. These inflammatory indices did not demonstrate statistically significant differences between psoriasis patients and controls (p > 0.05).Conclusion
No significant associations were observed between psoriasis severity and inflammatory hematological indices (NLR, PLR, SII) or vitamin deficiencies. These findings suggest limited standalone utility of these biomarkers for routine assessment of psoriasis severity in this retrospective cohort.Weiterlesen
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Psoriasis is a non-communicable inflammatory skin disease that affects approximately 2%-3% of the world's population. Given its high impact on quality of life and the fact that a subset of patients exhibits suboptimal or secondary loss of response to current treatments, identifying new therapeutic strategies is crucial. Proliferation-associated protein 2G4 (PA2G4) is a transcription factor that has been exclusively studied in cancer research, where it promotes cell growth and enhances tumourigenesis by inhibiting apoptosis. However, its role in inflammatory skin diseases remains largely unknown.Objectives
This study focused on the pathophysiological and immunological functions of PA2G4 in psoriasis and evaluated its potential as a therapeutic target.Methods
Bulk, single-cell, and spatial RNA sequencing combined with immunohistochemistry were used to assess PA2G4 expression in psoriatic skin compared with that in non-lesional controls. Functional studies were performed in primary human keratinocytes and reconstructed human epidermis (RHE) models using the CRISPR/Cas9-mediated knockout (KO) of PA2G4 and pharmacological inhibition of PA2G4 with the small-molecule WS6. The regulatory effects of PA2G4 on cellular processes, such as proliferation, differentiation, and survival, were investigated using RNA-seq, western blot analysis, scratch assays, and annexin V staining.Results
PA2G4 was highly abundant in psoriasis, and its expression was predominantly restricted to basal proliferating keratinocytes. Its gene expression is positively correlated with psoriasis severity, the degree of acanthosis, neutrophil infiltration, and genes which are upregulated in psoriasis. PA2G4 KO in primary human keratinocytes activated differentiation pathways while suppressing proliferation pathways, resulting in the downregulation of proliferation- and inflammation-related genes (e.g. MKI67, IL20, VEGFA, and HIF1A) and the upregulation of differentiation and cell adhesion markers (e.g. KRT6C, LCE2C, and DSG4). Functionally, the PA2G4 KO reduced keratinocyte proliferation in scratch assays, attenuated interleukin-22-induced acanthosis in RHE models, and promoted keratinocyte death. Pharmacological inhibition of PA2G4 using the small-molecule inhibitor WS6 similarly downregulated genes associated with proliferation and cell survival.Conclusions
PA2G4 could promote keratinocyte hyperproliferation and survival in psoriasis, thereby critically influencing epidermal homeostasis. Therefore, inhibition of PA2G4 may represent a new treatment option for psoriasis.Weiterlesen
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Psoriasis, a chronic inflammatory skin disease affecting 2-3% of the global population, is driven by dysregulated immune responses. Despite advancements in biologic therapies, treatment challenges persist due to high recurrence rates. This study aimed to identify immune-related hub genes and elucidate their clinical implications in psoriasis pathogenesis and therapy.Methods
Multiple microarray datasets from psoriasis patients (GSE30999, GSE106992, GSE14905, GSE78097, and GSE117468) were obtained to identify immune-key genes by differential gene analysis and Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, immune-related hub genes were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Protein-Protein Interaction (PPI) networks, with further validation through Gene Set Enrichment Analysis (GSEA) and Receiver Operating Characteristic (ROC) curves to assess exploratory within-sample discrimination. Pearson correlation analysis evaluated the relationship between hub genes, skin lesion severity, and treatment outcomes. The study also conducted immune infiltration by using the Cell-type Identification by Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm and identified potential therapeutic targets by the Drug-Gene Interaction Database (DGIdb).Results
Thirty-one immune-related key genes were identified, and six hub genes (CLEC7A, CXCL1, IRF1, S100A12, S100A8, S100A9) were validated as central players in immune signaling pathways. These genes exhibited within-sample discrimination (AUC > 0.9) and correlated with disease severity and biological therapy efficacy. Immune infiltration analysis revealed increased activated memory CD4+ T cells and M1 macrophages in lesional skin, which was strongly associated with hub gene expression. Additionally, drug-gene interaction analysis identified potential therapeutic agents targeting these genes.Conclusion
This study identified six immune-related hub genes that were closely linked to the severity of psoriasis, the effectiveness of biological treatments, and infiltrated activated memory CD4+ T cells and M1 macrophages. Our findings elucidate a novel immune-related hub gene network in psoriasis and provide potential targets for the development and application of biologics.Weiterlesen
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Evidence-based recommendations for the treatment of patients with psoriatic disease (PsO) and a prior history of malignancy are limited. This study aimed to compare the incidence of newly diagnosed neoplasms among patients with PsO and a previous malignancy receiving treatment with conventional systemic therapies, apremilast, or biologic agents.Patients and methods
Retrospective observational study using TriNetX. PsO patients (ICD10:L40) with a previous diagnosis of cancer (ICD10:C00-D49) less than 5 years prior to systemic therapy initiation were selected. Outcomes evaluated included new documentation of neoplasms and all-cause mortality.Results
Patients under biologic therapy had a significantly lower new neoplasm documentation rate and all-cause mortality compared to classical agents (HR 0.857 and HR 0.705, respectively) and apremilast (HR 0.782 and HR 0.803, respectively) at 3 years follow-up. Only TNFi exhibited a significantly lower new neoplasm rate (HR 0.867, p < 0.0001) compared to classical agents; however, all biologic agents significantly decreased mortality. IL-23i was the only biologic therapy to significantly lower cancer recurrence risk (RR 0.878) compared to TNFi, with no differences in all-cause mortality.Conclusions
Biologic therapy for PsO may represent a safe treatment option in patients with a history of malignancy, compared with conventional systemic therapies or apremilast. Among biologic agents, IL-23 inhibitors appear to be associated with the most favorable safety profile.Weiterlesen
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There is very limited data regarding atlantoaxial instability (AAI) in patients with psoriatic arthritis (axPsA). In this study, we aimed to contribute to the existing literature on this topic.Methods
Adult patients were included in this single-center study who were classified as PsA by the 'CASPAR' criteria and evaluated as having axial involvement according to the 'Calin' criteria. Those with inflammatory or non-inflammatory diseases that could affect the spine were excluded. Electronic patient files were reviewed retrospectively. Lateral neutral/full extension/full flexion and open-mouth anteroposterior cervical radiographs were evaluated by three rheumatologists blinded to the patients. Patients were compared in two groups as AAI-positive and AAI-negative.Results
A total of 100 patients with a mean age of 48.8 years and a mean PsA duration of 7.4 years, 57% of whom were female, were included in the study. A total of 20 AAI lesions were detected in 18% patients; subaxial subluxation was detected in eight, anterior atlantoaxial subluxation (AAS) in seven, posterior AAS in three, lateral AAS in one, and vertical subluxation in one case. In the group with AAI, the presence of psoriasis (Ps) (p = 0.037), scalp psoriasis (p < 0.001), and the use of targeted therapy for Ps and PsA (p < 0.001, p < 0.001) were significantly higher than in the AAI-negative group.Conclusion
Given that Ps and PsA patients on targeted therapy may reflect cases with higher disease activity and inadequate response to conventional treatments, it may be appropriate to consider closer monitoring for AAI in these patients. Key Points • Atlantoaxial instability is present in approximately one-fifth of patients with axial psoriatic arthritis. • The most common instability lesion is subaxial subluxation, accounting for 40% of all lesions. • The presence of psoriasis, scalp psoriasis, and the use of targeted therapies for psoriatic arthritis or psoriasis are significantly more frequent in the group with atlantoaxial instability. These factors may be useful for cervical spine monitoring in patients with axial psoriatic arthritis. • The use of targeted therapies for psoriatic arthritis or psoriasis may indirectly indicate an association between high disease activity and atlantoaxial instability.Weiterlesen
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