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Neue Studien
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Psoriasis patients frequently present with cardiovascular comorbidities, which maybe associated with abnormal epicardial adipose tissue (EAT). This study aimed to evaluate the predictive value of radiomics features derived from non-contrast chest CT (NCCT) combined with serological parameters for identifying abnormal EAT in psoriasis.Methods
In this retrospective case-control study, we enrolled consecutive psoriasis patients who underwent chest NCCT between September 2021 and February 2024, along with a matched healthy control group. Psoriasis patients were stratified into mild-to-moderate (PASI ≤ 10) and severe (PASI > 10) groups based on the Psoriasis Area and Severity Index (PASI). Using TIMESlice, we extracted EAT volume, CT values, and 86 radiomics features. The cohort was randomly divided into a training (70%) and test (30%) set. LASSO regression selected radiomic features to calculate the Rad_Score. Serum uric acid (UA) and C-reactive protein (CRP) levels were collected. We compared EAT volume, CT values, Rad_Score, UA, and CRP between groups and developed three models: Model A (UA, CRP, EAT CT values), Model B (Rad_Score), and Model C (UA, CRP, EAT CT values, Rad_Score). Model accuracy was evaluated using ROC curves (P < 0.05).Results
The study included 77 psoriasis patients and 76 matched controls. Psoriasis patients had higher UA and CRP levels than controls (both P < 0.001). EAT CT value was higher in psoriasis (P = 0.020), with no volume difference. Eight radiomics features and Rad_Score significantly differed between groups (P < 0.001), and Rad_Score also higher in severe group than that in mild-to-moderate group (P < 0.001). Model C showed the highest AUC in both sets: training 0.947 and test 0.895, indicating superior predictive performance.Conclusions
Combining radiomics features, EAT CT values, UA, and CRP in a predictive model accurately predicts EAT abnormalities in psoriasis, potentially improving cardiovascular comorbidity diagnosis.Clinical trial number
Not applicable.Weiterlesen
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The International Psoriasis Council (IPC) reclassified patients eligible for systemic therapy to include those with body surface area (BSA) > 10%, psoriasis lesions in high-impact areas, or failure of topical therapy. Risankizumab is an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis. This retrospective study evaluated the real-world effectiveness of risankizumab in patients with BSA 3-10% and patients meeting IPC systemic therapy criteria, addressing existing gaps in knowledge regarding its effectiveness in these patient groups.Methods
Biologic-naïve adults with moderate-to-severe plaque psoriasis who initiated risankizumab between April 2019 and August 2023 and were treated for 12 (± 3) months were identified from the CorEvitas Psoriasis Registry and stratified by baseline BSA. At 12 months, skin clearance was assessed by achievement of Psoriasis Area Severity Index (PASI) 90, PASI 100, and National Psoriasis Foundation (NPF) treat-to-target goals. Patient-reported outcomes (PROs) included achievement of Dermatology Life Quality Index (DLQI) 0/1, improvements in psoriasis symptoms, and work and activity impairment.Results
Of 272 patients analyzed, 123 had BSA 3-10% (78 had any high-impact area involvement and 105 had prior topical therapy experience) and 149 patients had BSA > 10%. Among those with BSA 3-10%, 77.9% achieved PASI 90 and 67.2% achieved PASI 100. NPF acceptable and target responses were met by 95.3% and 87.9%, respectively. Regarding PROs, 68.1% of patients with moderate skin involvement (BSA 3-10%) attained a DLQI score of 0/1. Significant improvements from baseline in psoriasis symptoms and reductions in work and life impairments were also reported (P < .001). Comparable positive outcomes were observed across all IPC systemic therapy eligible patient subgroups.Conclusion
In patients with BSA 3-10% and those systemic-eligible per IPC classification, continuous treatment with risankizumab for 12 months resulted in high levels of skin clearance and improvements in PROs.Weiterlesen
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Placebo effects are a significant challenge in the conduct of clinical trials. We explored how global recruitment patterns influence the extent of placebo responses in randomized controlled trials of psoriatic arthritis and plaque psoriasis.Methods
We conducted an analysis of 51 trials (6,843 patients; 52±5.7% female) in psoriatic arthritis, and 43 trials (5,671 patients; 32±7.1% female) in plaque psoriasis investigating biological and targeted synthetic therapeutics. We investigated to what extent global recruitment patterns are related to the extent of response rates in the placebo arms of these clinical trials by investigating underlying socioeconomic factors using the average per capita gross national income (GNI; weighted for recruiting study centers per country) as proxy of these patterns in linear mixed models.Findings
We identified a negative association of GNI and placebo response rates on the primary endpoints across psoriatic arthritis trials (ACR20: β=-5.7% per 10,000 international Dollars; 95% CI: -7.8% to -3.5%; p<0.001) and plaque psoriasis trials (PASI75%: β=-1.1%; 95% CI: -2.0 to -0.3; p=0.011). Sensitivity analyses using other outcome measures and alternative economic metrics, such as the UN Human Development Index and WHO out-of-pocket health expenditures were confirmatory.Interpretation
The global expansion of trial recruitment to less affluent countries may increase placebo rates in studies of psoriatic arthritis and plaque psoriasis. These higher placebo rates may reflect the higher perceived benefit in these countries, leading to regression to the mean after patients have been successfully enrolled.Weiterlesen
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Psoriasis is an inflammatory disorder characterized by scaly erythematous plaques and significant comorbidities. Recent studies have suggested that impaired mitophagy, the cellular mechanism for removing dysfunctional mitochondria, may contribute to the pathogenesis of psoriasis.Methods
In this study, we analyzed bulk RNA sequencing data from 167 healthy individuals and 177 patients with psoriasis obtained from the Gene Expression Omnibus database (GSE30999 and GSE54456). Mitophagy-related genes were isolated using weighted gene co-expression network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed and protein-protein interaction networks were constructed for the functional enrichment of genes associated with mitophagy. The correlations between genes associated with mitophagy, signaling pathways, and immune cell infiltration were analyzed. The potential diagnostic value of genes associated with mitophagy was evaluated using receiver operating characteristic (ROC) curves, which were validated in imiquimod-induced psoriatic skin lesions in mice.Results
We identified 3,839 differentially expressed genes between healthy individuals and patients with psoriasis, and 23 genes were selected as hub genes showing a high correlation with mitophagy in psoriasis. GO and KEGG analyses revealed that hub and associated genes were significantly correlated with skin functions, such as epidermal development and keratinocyte differentiation. In addition, mitophagy-related genes were negatively associated with pro-inflammatory and pro-proliferation pathways in psoriasis. Among the immune cells, CD4+ T cells were most significantly affected by mitophagy-related genes. ROC analysis demonstrated that mitophagy-related genes, especially ACER1, C1ORF68, CST6, FLG2, GJB3, GJB5, GPRIN2, KRT2, and SPRR4 were potential biomarkers of psoriasis for use in diagnosis or treatment.Conclusions
Mitophagy-related genes play crucial roles in psoriasis and have potential use as biomarkers, providing insights into disease mechanisms and therapeutic targets. Further research may lead to the development of new strategies for psoriasis management.Weiterlesen
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Conflicting data exist on TNF inhibitors' (TNFi) role in preventing psoriatic arthritis (PsA) in psoriasis. Using propensity score matching, we compared PsA incidence in severe psoriasis patients treated with TNFi versus narrow-band ultraviolet B (nbUVB) phototherapy over a decade of follow up.Methods
Consecutive adults with severe psoriasis prescribed TNFi or nbUVB phototherapy between September 2005 and September 2010 were enrolled. Of 946 patients, 497 received TNFi (median follow-up 9.6±2.6 years) and 449 underwent nbUVB (9.4±5.9 years). All had rheumatologist assessment before therapy and for PsA diagnosis. PS matching adjusted for factors linked to PsA, including arthralgia, family history, BMI, PASI, and psoriasis distribution, including nails.Results
After propensity score matching, the TNFi cohort contributed 2705.5 person-years of follow-up (mean 9.1 ± 2.9 years), and the nbUVB cohort 2654.1 person-years (mean 8.9 ± 5.4 years). The PsA incidence rate per 100 patients was 1.18 (0.84-1.52) in the TNFi group and 2.48 (2.24-2.72) in the nbUVB group, yielding an incidence rate ratio of 2.1 (1.37-2.98, p = 0.0002). A time-dependent Cox model confirmed that TNFi treatment was associated with a significantly lower risk of PsA (HR = 0.32, p < 0.0001). Arthralgia (HR = 7.68, p < 0.0001), nail psoriasis (HR = 1.93, p = 0.0004), and higher PASI score (HR = 1.03 per point, p = 0.0096) were independent predictors of PsA.Conclusion
This PS-matched study shows a clear benefit of TNFi versus nbUVB in PsA reduction in severe psoriasis patients over nearly a decade of therapy.Weiterlesen
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Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory arthritis that develops in 30% of patients with psoriasis, leading to increased morbidity and mortality and reduced quality of life. MicroRNAs (miRNAs) modulate gene expression and have been associated with the pathogenesis of immune-mediated disorders. We aimed to identify miRNAs that can be used as biomarkers for the development of PsA in patients with psoriasis.Methods
miRNA expression levels were assessed in serum samples from 28 patients with PsA, 35 patients with cutaneous psoriasis without arthritis (PsC), and 28 healthy controls through next-generation sequencing. Differential expression was assessed by linear modeling with empirical Bayes moderation corrected for sequencing batch, age, sex, and duration of psoriasis. For validation, we measured the expression of >191 genes predicted to be targeted by the dysregulated miRNAs using a custom NanoString probe panel in an independent cohort of 144 patients with PsA and 88 patients with PsC. The enrichment of specific pathways corresponding to the differentially expressed gene targets was examined using pathDIP.Results
In the discovery cohort, the miRNA miR-190a-5p was significantly down-regulated in patients with PsA compared to those with PsC (P< 0.05), and both miR-190a-5p and miR-26b-5p were down-regulated in patients with PsA versus healthy controls (P < 0.05). In the validation cohort, 26 gene targets of both of these miRNAs were differentially expressed. These genes were enriched in signaling pathways associated with bone formation and regeneration: Wnt and transforming growth factor β.Conclusion
Serum expression levels of miR-190a-5p and miR-26b-5p can potentially serve as biomarkers for PsA development.Weiterlesen
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Little is known about the ideal service delivery model and shortcomings in patient experiences in the NHS for patients with psoriatic arthritis (PsA). The objective of this work was to identify unmet needs perceived within the current health service delivery model for PsA from the UK Psoriatic Arthritis Priority Setting Partnership (PsA-PSP).Methods
An online survey was conducted in 2020 and distributed to people with PsA, their carers and clinicians to identify research priorities in PsA. The participants were asked to submit three questions unanswered in PsA research. A proportion of submissions related to health service delivery were identified, which were deemed as out of scope for the main PsA-PSP but nevertheless important to report. Content analysis was used to analyse these submissions separately.Results
We reviewed 138 submissions that were not related to the James Lind PSP and research priorities in PsA. Among these, 118 (85.5%) were focused on health service delivery and were classified into five main themes: rheumatology service, primary care navigation, education, holistic care, and ethnicity, diversity and inclusion. Further analysis within the rheumatology service theme revealed additional sub-themes that emphasized integrating multidisciplinary services, improving access to advice lines and ensuring fair access to treatments.Conclusion
The five key themes provide valuable insights into the important areas of interest within health service delivery in the UK. By understanding these themes, policymakers, healthcare providers and researchers can better prioritize their efforts and address the specific care needs of people with PsA, their care providers and clinicians.Weiterlesen
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Generalized pustular psoriasis in a patient with asthma following dupilumab and tezepelumab therapy.
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Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with psoriasis and characterised by heterogeneous clinical manifestations, including peripheral and axial arthritis, enthesitis and dactylitis. A subset of patients exhibits a 'difficult-to-treat' (D2T) phenotype, necessitating complex therapeutic strategies. Metabolic syndrome (MetS) is highly prevalent in PsA patients and has been implicated in increased disease activity.This study aimed to evaluate the impact of MetS on the development of D2T phenotype in PsA and its potential implications for disease management.Methods
A cross-sectional study was conducted on PsA patients recruited from the Rheumatology Clinic at Fondazione Policlinico Campus Bio-Medico of Rome. Patients fulfilling the Classification Criteria for Psoriatic Arthritis criteria were assessed for disease activity and the presence of MetS according to National Cholesterol Education Programme Adult Treatment Panel III criteria. D2T PsA was defined based on the Rheumatoid Arthritis European Alliance of Associations for Rheumatolog criteria revised for PsA by Perrotta et al. Statistical analyses, including logistic regression and path analysis, were performed to explore associations between MetS and D2T PsA.Results
Among 182 PsA patients, 42.94% met MetS criteria. The D2T subset (n=66) demonstrated a significantly higher prevalence of MetS (81.82% vs 29.37%, p<0.0001). Logistic regression revealed a strong association between MetS and D2T PsA (OR 7.56, 95% CI 2.53 to 22.56, p<0.0001), and path analysis confirmed MetS as an independent predictor of D2T phenotype.Conclusions
MetS is strongly associated with a D2T phenotype in PsA, suggesting that metabolic comorbidities contribute to disease severity and treatment resistance. Addressing metabolic dysfunction may be crucial in optimising therapeutic outcomes in PsA management.Weiterlesen
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The mechanism of action of treatment drugs for psoriasis is based on anti-inflammation and the inhibition of epidermal proliferation, and retinoids and vitamin D3 derivatives are first-line therapy drugs for psoriasis. This meta-analysis aimed to comprehensively evaluate the efficacy and safety of calcipotriol-acitretin combination therapy for psoriasis and investigate its effect on serum inflammatory factors.Methods
A systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese biomedical literature service system (SinoMed), and Chinese Biomedical Journal Database (VIP), from the earliest record until Dec.13, 2024, was conducted. The outcomes were overall effective rate, Psoriasis Area and Severity Index (PASI) scores, inflammatory factor level and side effects.Results
A total of 13 studies with 1196 patients were included in this meta-analysis. The results of this study show that the calcipotriol-acitretin combination therapy could improve the total effective rate when compared with acitretin [RR = 1.25, 95% CI (1.18, 1.33)] or calcipotriol [RR = 1.36, 95% CI (1.20, 1.56)] monotherapy. The combined therapy could decrease the PASI score observably when compared with acitretin monotherapy [SMD = - 2.26, 95% CI (-3.24, -1.28)] or calcipotriol monotherapy [SMD = - 3.79, 95% CI (-5.78, -1.79)]. Calcipotriol-acitretin combination therapy remarkably reduced the levels of TNF-α, IL-23, IL-17, INF-γ and IL-6 in serum, while increasing the levels of IL-4 and IL-10 within the serum, compared to acitretin monotherapy. This combination therapy did not increase the risk of skin irritation & burning pain, dry skin and perioral dermatitis. Notably, the incidence of perioral dermatitis was lower in combination therapy than acitretin monotherapy [P = 0.04, RR = 0.24, 95% CI (0.06, 0.93)].Conclusions
The calcipotriol-acitretin combination therapy could be a safe and effective therapeutic strategy in the treatment of psoriasis. However, the lack of PROSPERO registration and the high heterogeneity in this study limited the conclusion, and more high-quality RCTs were needed for further evaluation.Weiterlesen
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Psoriasis is a chronic inflammatory skin disorder characterized by elevated levels of proinflammatory cytokines. Mesenchymal stem cells (MSCs) have demonstrated therapeutic potential, yet the specific mechanisms involved are not fully understood.Objective
To investigated the effectiveness of extracellular vesicles (EVs) derived from MSCs that were genetically modified to overexpress miR-146a, in a mouse model of psoriasis.Methods
To enhance miR-146a expression, MSCs were transfected, and their EVs were subsequently purified. Thirty mice were randomly assigned to three groups and induced with imiquimod cream to develop psoriasis-like skin lesions. The treatment groups included: (1) a control group administered PBS, (2) a group treated with EVs containing a control miRNA (miR-control EVs), and (3) a group receiving EVs enriched with miR-146a (miR-146a-EVs). EVs were administered intravenously and lesions were evaluated. Following intravenous administration of EVs, the severity of skin lesions was assessed. Concentrations of key cytokines, including IFN-γ, IL-17, TNF-α, IL-23, IL-6, IL-1β, TGF-β, IL-10, and IL-4, were quantified in both spleen and skin tissue lysates using ELISA and qRT-PCR techniques.Results
The experimental findings demonstrated that the administration of miR-146a-enriched EVs led to a significant improvement in clinical symptoms. There were substantial reductions observed in combined erythema, scaling, and skin thickness measurements compared to untreated controls. Additionally, levels of proinflammatory cytokines IFN-γ, IL-17, TNF-α, IL-23, IL-6, and IL-1β were significantly downregulated in the miR-146a-EV group, while anti-inflammatory TGF-β, IL-10 and IL-4 were upregulated. The same results were obtained in the spleens of mice.Conclusion
EVs derived from miR-146a-modified MSCs effectively reduced psoriasis-like inflammation by modulating cytokine expression. This novel cell-free therapy holds promise for the treatment of psoriasis.Weiterlesen
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Psoriatic arthritis (PsA) is an immune-inflammatory disease involving skin and synovial-entheseal compartments. The understanding of IL-17 biological function has revolutionized the understanding of PsA pathogenesis and, consequently, its therapeutic approach.Areas covered
In this review article, we have outlined the primary evidence regarding the biological functions of IL-17A in PsA, and summarized data from randomized controlled trials (RCTs) on PsA and psoriasis approved secukinumab, ixekizumab, bimekizumab, brodalumab, and emerging IL-17 inhibitors.Expert opinion
The biologic disease-modifying antirheumatic drugs (bDMARDs), secukinumab, and ixekizumab target interleukin-17A (IL-17A), and bimekizumab, which simultaneously neutralizes IL-17A and IL-17F, have demonstrated efficacy in treating both peripheral and axial articular manifestations of PsA, as well in improving skin involvement, enthesitis and dactylitis. Brodalumab, which inhibits the IL-17 receptor A (IL-17RA), represent an efficacious strategy for psoriasis.Continued research into the role of IL-17s in PsA pathogenesis is crucial for improving our understanding of the disease and developing more effective therapeutic strategies. Further research and advancements in biologic therapies will refine IL-17 inhibitory strategies, potentially improving outcomes for PsA patients, and other immune-mediated diseases.Weiterlesen
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