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Psoriasis is a chronic immune-mediated disease with significant systemic implications. Tildrakizumab, an IL-23p19 inhibitor, has demonstrated efficacy in moderate-to-severe plaque psoriasis. Higher doses may be beneficial for patients with elevated body weight or greater disease burden. This study evaluates the effectiveness of tildrakizumab 200 mg in a real-world setting, analyzing outcomes based on weight, Psoriasis Area Severity Index (PASI), body mass index (BMI), and prior biologic exposure.Methods
A multicenter retrospective study was conducted across 10 Italian hospitals. Adult patients (≥ 18 years) with moderate-to-severe plaque psoriasis treated with tildrakizumab 200 mg for ≥ 36 weeks were included. Patients were stratified by weight (≥ 90 kg vs. < 90 kg), BMI (≥ 30 vs. < 30), PASI (≥ 15 vs. < 15), and biologic history (naïve vs. biologic (bio)-experienced). PASI100 response rates at 36 weeks were assessed. Statistical analyses included Fisher's exact test (p < 0.05 significant).Results
Among 137 patients, PASI100 response rates were 67.1% for patients < 90 kg vs. 49.2% for ≥ 90 kg (p = 0.04), 61.5% for PASI < 15 vs. 50% for PASI ≥ 15 (p = 0.03), and 60.8% for bio-naïve vs. 57.1% for bio-experienced (p = 0.08). BMI ≥ 30 was associated with lower PASI100 (44.2%) compared to BMI < 30 (61.4%) (p = 0.05). Despite subgroup differences, all patients exhibited clinical improvement.Conclusion
Tildrakizumab 200 mg effectively treated moderate-to-severe psoriasis across diverse patient subgroups. While higher weight and PASI were associated with slightly lower PASI100 rates, significant improvements were observed, supporting its role in difficult-to-treat patients.Weiterlesen
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Flexible biologic therapy dosing regimens in psoriasis management are common, but data from routine care in Germany are scarce. This study evaluated treatment adjustments for biologic therapies commonly prescribed in Germany.Patients and methods
Charts for up to 100 consecutive patients treated at 29 centers were reviewed. Data were extracted for adults (aged 18-65 years) with moderate-to-severe plaque psoriasis treated with adalimumab, guselkumab, ixekizumab, secukinumab, or ustekinumab for ≥ 36 weeks. The primary endpoint was time to first treatment adjustment. Secondary endpoints included frequency of and reasons for treatment adjustments. Time to treatment adjustment was analyzed using Kaplan-Meier methods.Results
Among 982 patients, 297 treatment adjustments in 240 (24.4%) patients were identified. The mean (median; interquartile range) time to first treatment adjustment (n = 223) was 8.4 (4.0; 2.0-12.0) months (secukinumab: 14.1 [10.0; 4.0-21.0], adalimumab: 11.0 [7.0; 3.0-14.5], ustekinumab: 11.0 [6.0; 2.0-16.0], ixekizumab: 5.8 [3.0; 2.0-8.5], guselkumab: 5.1 [3.0; 2.0-7.0]). The most frequent adjustment type was starting concomitant treatment(s) (10.4% of patients); insufficient skin effectiveness was the most frequent reason for adjustment.Conclusions
Biological treatment adjustments are frequent in moderate-to-severe psoriasis; flexible dosing regimens would support optimal management.Weiterlesen
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Psoriasis is a chronic inflammatory skin condition driven by immune dysregulation, significantly diminishing patients' quality of life. The advent of targeted biological therapies and small molecule inhibitors has transformed the treatment landscape for moderate-to-severe Psoriasis. Nevertheless, there remains a scarcity of comparative efficacy and safety data between these therapeutic classes, highlighting the need for a systematic review to evaluate their relative performance.Objectives
This systematic review seeks to consolidate evidence from comparative studies that assess the effectiveness and safety of biologic agents and small molecule inhibitors in managing moderate-to-severe Psoriasis. The aim is to provide a well-founded, evidence-based perspective on the most effective therapeutic approaches by analysing their efficacy, safety profiles, and long-term treatment durability.Methods
An extensive literature search was conducted across Web of Science, PubMed, and Scopus to identify randomised clinical trials (RCTs) comparing biologics and small molecule inhibitors. Inclusion criteria required that the RCTs be published in English, with full-text availability and a primary focus on treatment efficacy and safety outcomes. Studies were excluded if they were retrospective, observational, case reports, or non-English publications. Study selection and data extraction were carried out independently by two reviewers, with disagreements resolved by a third reviewer.Results
A total of 22 head-to-head RCTs, encompassing over 50,000 patients, met the inclusion criteria. Biologic therapies targeting IL-17 (Secukinumab, Ixekizumab, Brodalumab), IL-23 (Guselkumab, Risankizumab, Tildrakizumab), and TNF-α (Adalimumab, Etanercept) exhibited superior efficacy compared to conventional systemic treatments. Secukinumab consistently surpassed Ustekinumab in achieving PASI 90 and PASI 100 responses. Guselkumab demonstrated sustained superiority over Adalimumab, yielding higher rates of skin clearance at Week 48. Similarly, Risankizumab delivered superior long-term PASI 90 responses when compared to Secukinumab. Among small molecule inhibitors, Deucravacitinib proved more effective than Apremilast in achieving PASI 75 and static Physician Global Assessment responses. Safety profiles were generally comparable across the treatment groups, although IL-17 inhibitors were associated with a higher incidence of Candida infections.Conclusions
This systematic review highlights the enhanced efficacy of IL-17 and IL-23 inhibitors compared to TNF-α inhibitors, with IL-23-targeting agents demonstrating superior long-term disease control. Small molecule inhibitors, particularly Deucravacitinib, present a promising alternative as effective oral therapies. Although newer biologics offer improved treatment outcomes, further head-to-head trials comparing TYK2, JAK, and PDE4 inhibitors with IL-17 and IL-23 agents are warranted. These findings provide valuable insights to inform clinical decision-making and optimise Psoriasis management strategies.Weiterlesen
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Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease that causes chronic pain, psychological problems, and a significant economic burden, and therefore must be diagnosed and treated early. Existing treatments have limited efficacy and side effects. The study aimed to identify potential drug targets associated with psoriatic arthritis through proteomics and Mendelian randomization (MR) analysis.Materials and methods
Large-scale genome-wide association studies and proteomics data were used to assess the causal relationship between plasma proteins and PsA through MR analysis, Bayesian colocalization analysis, summary data-based Mendelian randomization (SMR) analysis, and heterogeneity in dependent instruments (HEIDI) test, and to analyze protein-protein interaction networks.Results
The study identified 26 proteins that may be causally related to PsA, of which 15 were positively correlated and 11 negatively correlated. According to the results of SMR analysis and colocalization analysis, these targets were further analyzed and classified into high, medium, and low confidence levels. High confidence targets include APOF, PRSS27, and DDX58, which were consistently supported by multiple analyses.Conclusion
The study identified several promising targets for the treatment of psoriatic arthritis through multiple analysis methods, providing a theoretical basis for future treatment strategies, but further experimental verification and clinical research are needed. Key Points • Using large-scale genome-wide association studies and proteomics data, drug targets for psoriatic arthritis (PsA) were identified through Mendelian randomization analysis, Bayesian colocalization analysis, and summary-data-based Mendelian randomization (SMR) analysis. • The study identified 26 proteins that are causally related to psoriatic arthritis, of which 15 are positively and 11 are negatively associated with psoriatic arthritis. • Among the identified proteins, APOF, PRSS27, and DDX58 were ranked as high confidence targets.Weiterlesen
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The correlation between psoriasis with individual cardiometabolic diseases (CMDs), including coronary heart disease (CHD), stroke, hypertension, heart failure (HF), and type 2 diabetes mellitus (T2DM), have yielded conflicting results, and genetic susceptibility's role in modifying these relationships remains unexplored.Objective
To investigate the association of psoriasis with the risk of CMDs, and to assess the modified effect of genetic susceptibility on these associations.Methods
A total of 390,165 participants from the UK Biobank cohort were enrolled. Cox proportional hazards models were used to examine the association between psoriasis and the incidence of CMDs. The genetic risk score for these diseases was incorporated as tertiles to assess potential effect modification in these association. The outcome was CMDs.Results
During a median 12.0-year follow-up, a total of 23,811 incident CHD events, 6,941 HF, 82,963 hypertension, 6,902 stroke, and 16,788 T2DM were recorded. Participants with psoriasis had an increased risk of incident CHD (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.21), HF (HR 1.20, 95% CI 1.06-1.35), hypertension (HR 1.10, 95% CI 1.05-1.15), and T2DM (HR 1.22, 95% CI 1.11-1.34) compared to those without psoriasis. The adverse impact of psoriasis was pronounced among individuals with a high genetic predisposition. The elevated risk of CMDs associated with psoriasis may be partially explained by inflammation and dyslipidemia.Conclusions
Psoriasis was associated with the incidence of CMDs, particularly among individuals with higher genetic predisposition. Hence, our study emphasized the significance of preventing and managing CMDs among psoriasis patients, particularly those with high genetic risk.Weiterlesen
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Psoriasis is a chronic disease with a prevalence of 3% in the general population. The high prevalence of psoriasis has prompted the study of its comorbidities in recent decades. However, no studies have ever analyzed comorbidity patterns including all chronic diseases in psoriatic patients.Objectives
To identify comorbidity patterns in psoriatic patients using network analysis and describe them from a clinical point of view.Methods
We conducted an observational and retrospective study with individuals of the EpiChron Cohort (Aragón, Spain) diagnosed with psoriasis from January 1st, 2010 through December 31st, 2019. The population was stratified by sex and age intervals (0-11, 12-17, 18-44, 45-64 > 65). We built a network for each stratum (ie, 5 for each sex), calculating the tetrachoric correlations of each pair of diseases. We used a cut-off threshold for statistical significance of p-value < 0.01. We applied the Louvain community detection algorithm to identify clusters of diseases.Results
The prevalence of psoriasis in Aragón was found to be 2.84%. We identified a total of 31,178 psoriatic patients (54% men, 61% from metropolitan areas). The most common comorbidities were respiratory diseases, cardiometabolic conditions (such as hypertension and dyslipidemia), and mental health disorders (including anxiety and mood disorders). A total of 21 comorbidity patterns were identified, varying by sex and age group.Conclusions
This is the first study ever conducted with a comprehensive analysis of the disease patterns of psoriatic patients. Our results are a comprehensive map of possible psoriasis-related comorbidities. Further studies should confirm these associations and their pathophysiological relationship with psoriasis, which could help to detect and prevent comorbidities and modifiable risk factors.Weiterlesen
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Psoriasis is an immune-mediated skin disease where Th17 cell differentiation and IL-17 secretion play critical roles. This study investigates key exosomal ncRNAs regulating the Th17/IL-17 axis in psoriasis and their mechanisms.Methods
We integrated bulk RNA sequencing datasets from the GEO database to construct and evaluate exosome-related patterns. Subsequently, exosome-related ncRNAs in psoriasis lesions were identified primarily through weighted gene co-expression network analysis and five machine learning algorithms. Additionally, large-scale integrated single-cell RNA sequencing data and genome-wide association study (GWAS) data were included to investigate the mechanisms of key ncRNA, primarily through immune infiltration analysis, gene set enrichment analysis (GSEA), co-expression analysis, and Mendelian randomization. Finally, the mechanisms of key ncRNA were confirmed primarily through cell co-culture and lentiviral transfection, assessed by immunofluorescence, qRT-PCR, and Western blot.Results
We identified 10 exosome-related ncRNAs, including PRKCQ-AS1, and constructed five machine learning models with excellent diagnostic performance, emphasizing PRKCQ-AS1's significance. Mendelian randomization demonstrated a causal relationship between PRKCQ-AS1 and psoriasis. Immune infiltration analysis and GSEA indicated that PRKCQ-AS1 influences the infiltration pattern of CD4+T cells, promotes Th17 differentiation, and is related to STAT3. The expression distribution in single-cell RNA sequencing data suggested that exosomal PRKCQ-AS1 may originate from keratinocytes, and co-expression analysis supported its role in STAT3 activation within lymphocytes. Co-culture experiments confirmed that keratinocytes in psoriasis models, as well as keratinocytes overexpressing PRKCQ-AS1, can upregulate PRKCQ-AS1 levels in CD4+T cells via exosomes, promoting Th17 cell differentiation and IL-17 secretion. Consistent results and STAT3 signaling pathway activation were detected in CD4+T cells overexpressing PRKCQ-AS1.Conclusion
PRKCQ-AS1 is an exosomal lncRNA from keratinocytes in psoriasis, promoting Th17 differentiation and IL-17 secretion through STAT3 activation. This finding deepens the understanding of psoriasis pathogenesis and provides a basis for targeted therapies.Weiterlesen
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Psoriasis is a chronic disease and prevalent among 2-3% of the global population. Several therapeutic options alongside recent biologics have allowed the decrease and control of psoriasis lesions reaching a Psoriasis Area Severity Index (PASI) clearance of PASI75 or PASI90. Despite clinical improvements in lesions and provided PASI scores by clinicians as treatment success, patients have expressed varied satisfaction and perceptions. We present a case series that provides real-world evidence of combitherapy with calcipotriol and betamethasone dipropionate (Cal/BD) foam and biologics/systemics for the treatment of persistent psoriatic lesions.Methods
A retrospective, single-center study involving 10 patients was conducted from July to December 2023. Data were retrieved before initiation of the combitherapy and at the 6-month follow-up at the Centre Hospitalier Universitaire de Rennes Pontchaillou in France. Patients included were adults (≥ 18 years old), diagnosed with moderate to severe psoriasis by a dermatologist, and treated with Cal/BD foam as well as either biologics and/or systemics medication. Psoriasis severity and the dynamics of the treatments were described using mean (m)PASI, body surface area (BSA) %, sleep disturbance, patient satisfaction, dermatology life quality index (DLQI) scores and itch observation.Results
Patients were mostly male (n = 7), had a mean age of 53.3 years and psoriasis history of 13.0 years (missing data = 2). All patients were treated by biologics/systemics with Cal/BD combitherapy, and improved mPASI after six months (p < 0.001). Most patients had a reduced BSA (60.0%) (p = 0.024) and lowered itch (70.0%). Sleep disturbance reported by four patients was improved. Most patients reported an improved DLQI (mean score from 11.8 to 0.1). Patient satisfaction was positive.Conclusions
Our insight into treatment combinations of Cal/BD foam may present an opportunity to improve standard care and patient satisfaction for hard-to-treat and persistent psoriasis lesions.Weiterlesen
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Psoriasis is a chronic immune-mediated skin disease characterized by the infiltration of multiple inflammatory cells and abnormal differentiation of keratinocytes in the skin. The treatment of psoriasis is primarily based on immunosuppressive drugs; however, their long-term use can lead to various adverse effects. Euphorbia humifusa Willd. (EuH) is used in traditional Chinese medicine for its anti-inflammatory properties and effects on skin diseases such as psoriasis.Aim of the study
This study aimed to evaluate the anti-psoriasis effects of EuH extract, and explore its underlying mechanisms.Methods and materials
The main components of EuH extract were analyzed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technology. Then, we administered EuH extract to imiquimod-induced psoriasis mice for 6 consecutive days, and evaluated the effects according to the psoriasis area and severity index (PASI), spleen index, histological analysis, immunohistochemical and immunofluorescence staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and flow cytometry analysis. The potential mechanism was revealed using RNA sequencing (RNA-seq) and validated by target prediction, ELISA, qRT-PCR and western blot (WB) analysis.Results
The UPLC-QTOF-MS/MS analysis showed that phenolics were the essential components in the water extracts of EuH, including flavonoids, phenolic acids, and gallotannins. Treatment with EuH alleviated psoriatic symptoms including skin condition, high PASI scores (erythema, scaling, and thickness), and spleen index values in imiquimod-induced mice. EuH treatment also inhibited keratinocyte hyperproliferation, reduced epidermal thickness, reduced inflammatory cell infiltration into skin lesions, decreased the mRNA levels of inflammatory factors, and restored T and Treg cellular balance in the spleen. RNA-seq, ELISA, qRT-PCR and WB analyses indicated that EuH extract reduced the inflammatory response and keratinocyte hyperproliferation by inhibiting the IL-17 signaling pathway.Conclusions
Our findings suggest that EuH extract suppresses keratinocyte hyperproliferation and inflammation in psoriasis by inhibiting the IL-17 signaling pathway, supporting EuH as a potential treatment for psoriasis.Weiterlesen
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Erosions of the skin and mucous membranes with epidermal dysmaturation are a known side effect of cytostatic chemotherapy regimens and can also be observed during low-dose methotrexate (MTX) therapy. The study aimed to delineate the clinical and histopathological alterations.Patients and methods
A database search of the archive for dermatopathology was conducted, identifying 22 patients who developed epidermal dysmaturation on low-dose MTX. Clinical and laboratory changes, along with an array of histologic parameters were analyzed and statistically evaluated using SPSS.Results
Patients were predominantly female with a mean age of 69.1 years. The main indications were psoriasis vulgaris and rheumatoid arthritis. Clinically, patients mostly presented erosive plaques at the injection site, on mucosal surfaces, and disseminated lesions. Most patients showed normal laboratory values. Histopathologically, key findings included enlarged keratinocytes with pale cytoplasm and enlarged nuclei with prominent nucleoli, along with the degeneration of the basal layer. Consistent observations in the dermal compartment included infiltration of neutrophilic granulocytes, lymphocytes, and histiocytes.Conclusions
This study proposes clinicopathological criteria for the diagnosis of MTX-associated skin toxicity, aiming to increase awareness among clinicians and pathologists for early diagnosis. Early recognition can prevent potentially life-threatening progression.Weiterlesen
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To construct a predictive model for Psoriatic Arthritis (PsA) based on clinical and ultrasonic characteristics in patients with plaque psoriasis (PsP).Patients and methods
Demographic, clinical, and ultrasound data were collected from patients with PsP and PsA between May 2019 and December 2022.Results
A total of 212 patients with PsP and 123 with PsA in the training cohort, whereas the validation cohort comprised 91 patients with PsP and 49 with PsA. The multivariate logistic regression identified nail psoriasis (odds ratio [OR] 1.88, 95% CI: 1.07-3.29), synovitis (OR 18.23, 95% CI: 4.04-82.33), enthesitis (OR 3.71, 95% CI: 1.05-13.14), and bone erosion (OR 11.39, 95% CI: 3.05-42.63) as effective predictors for PsA. The area under the curve was 0.750 (95% CI, 0.691-0.806) and 0.804 (95% CI, 0.723-0.886) for the training and validation cohorts, respectively. The Hosmer-Lemeshow goodness-of-fit test showed good consistency for both the training cohort (p = 0.970) and the validation cohort (p = 0.967). Calibration curves also indicated good calibration for both cohorts. The DCA revealed that the predictive model had good clinical utility.Conclusions
We have developed a quantitative, intuitive, and convenient predictive model based on nail psoriasis, synovitis, enthesitis, and bone erosion to assess the risk of PsA in patients with plaque psoriasis.Weiterlesen
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