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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
- 223 Aufrufe
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
- 228 Aufrufe
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
- 270 Aufrufe
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 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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Patients with cutaneous lymphomas (CL) are at an increased risk of developing secondary malignancies. This study aimed to assess the frequency of association between CL and Kaposi sarcoma (KS) and to identify factors that may promote the co-occurrence of these two diseases.Patients and methods
On January 25, 2024, we conducted a systematic search of four electronic medical databases to identify all published cases of KS associated with CL. The clinical course and outcomes of these patients were summarized. For critical appraisal, we applied the JBI Checklist for Case Reports. The study was registered in the PROSPERO database (CRD42022313204).Results
A total of 40 articles reporting on 45 patients were assessed for eligibility. We included 27 cases in the final analysis (26 cutaneous T-cell lymphomas, 1 cutaneous B-cell lymphoma). In 71% of cases, the diagnosis of CL preceded KS. Nearly half (48%) of the patients had erythrodermic mycosis fungoides or Sézary syndrome. KS lesions were predominantly limited to the skin, with complete remission achieved in 53% of cases.Conclusions
The association between KS and CL is rare, limiting our study due to the small sample size and potential reporting bias. Skin-targeted therapies, a restricted T-cell repertoire, and impaired T-cell responses in erythrodermic CTCL patients may contribute to the development of KS.Weiterlesen
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Psoriasis skin lesions are generally thought to occur before psoriatic arthritis (PsA) develops. However, PsA may be challenging to diagnose in the absence of psoriasis and might be underdiagnosed when occurring before psoriasis. We tested the hypothesis that PsA may commonly occur before psoriasis, but without psoriasis skin lesions, is diagnosed as another form of arthritis.Methods
A single-center retrospective chart review was performed to identify patients with qualifying diagnoses from January 1, 2023, until December 31, 2023. This study was performed using electronic health records at a large tertiary care medical center. Inclusion criteria were (1) the presence of inflammatory or non-inflammatory arthritic conditions, (2) prior to the diagnosis of psoriasis, atopic dermatitis, or rosacea. Diagnoses were screened using International Classification of Diseases, Tenth Revision (ICD-10) codes.Results
During 2023, we identified 2780 patients with rosacea, 1672 with psoriasis, and 5195 patients with atopic dermatitis, of whom 436 had preceding arthritis (239 with psoriasis [14.3%], 189 with rosacea [6.8%], and 126 with eczema [2.4%, p < 0.0001]).Conclusions
Arthritic symptoms are common in psoriatic patients before psoriasis develops, and psoriasis skin lesions do not necessarily precede psoriatic arthritis.Weiterlesen
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SB17 is a ustekinumab (UST) biosimilar targeting interleukin-12/23 for treating immune-mediated inflammatory diseases (IMIDs). The development of UST biosimilars like SB17 may help address the high cost of innovator biologics, offering affordable alternatives without compromising efficacy or safety.Areas covered
This review encompasses the totality of evidence supporting SB17's similarity to UST, its regulatory approval, and indication extrapolation. It also discusses SB17's lower immunogenicity relative to UST.Expert opinion
The approval of UST biosimilars represents a significant advancement in managing chronic IMIDs including psoriasis, plaque psoriasis, psoriatic arthritis, Crohn's disease, and ulcerative colitis, providing cost-effective, efficacious alternatives. A randomized double-blind 28-week study involving over 500 patients with moderate-to-severe chronic plaque psoriasis demonstrated SB17's equivalence to UST, with more than 80% of patients achieving over 90% improvement in psoriasis severity indices. Treatment-emergent adverse events were comparable between SB17 and UST. Despite their potential to transform clinical outcomes, economic burdens, and drug utilization patterns, the adoption of UST biosimilars faces challenges, including concerns about equivalence and regulatory inconsistencies. Addressing these issues through education, consistent regulatory frameworks, real-world data, and ongoing monitoring is crucial for their successful integration into clinical practice.Weiterlesen
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Psoriasis and psoriatic arthritis are chronic autoimmune inflammatory conditions frequently associated with a range of comorbidities, including oncological diseases. Managing these conditions in patients with a history of cancer requires careful consideration of treatment efficacy and safety. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, has shown promise in the treatment of psoriasis and psoriatic arthritis. However, data on its use in oncological patients remain limited.Methods
This retrospective observational study evaluated the efficacy and safety of Apremilast in 79 patients with a history of cancer who were treated for psoriasis and/or psoriatic arthritis over a period of approximately five years. Clinical outcomes were assessed using the Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Visual Analog Scale for pain (PAIN VAS) to monitor disease severity, quality of life, and articular involvement, respectively. Regular oncological assessments were conducted concurrently with Apremilast therapy to ensure patient safety and identify potential interactions.Results
Over the five-year treatment period, significant improvements were observed in PASI, DLQI, and PAIN VAS scores, indicating effective management of both dermatological and articular symptoms. Patients reported enhanced quality of life and reduced pain levels, reflecting the therapeutic benefits of Apremilast. Oncological evaluations revealed no significant adverse interactions between Apremilast and the patients' cancer history or treatments, underscoring the drug's safety profile in this population.Conclusion
This study highlights the efficacy and safety of Apremilast as a treatment option for psoriasis and psoriatic arthritis in oncological patients. The findings support its role in improving disease outcomes and quality of life, emphasizing the importance of personalized treatment strategies in managing complex cases involving a history of cancer. Further research is warranted to validate these results in larger patient cohorts.Weiterlesen
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Nail psoriasis (NP) is not an uncommon psoriasis variant whose symptoms have a negative impact on patients' quality of life. Treating NP can be a great challenge for the dermatologist, especially when it is presented as isolated subtype or when it is not associated with psoriatic arthritis (PsA). The available treatments, topical or systemic therapies, have limited efficacy and can be associated with adverse effects (AEs). Topical roflumilast is an FDA-approved treatment for skin plaque-psoriasis in patients aged 6 and above, but there is limited evidence for treating NP. We present outcomes of nail psoriasis not associated with PsA treated with roflumilast 0.3% cream in 7 patients.Methods
A single center, retrospective case series analysis was conducted in a Canadian nail clinic in adult patients with NP refractory to treatment between January 2023 and December 2024. Clinical characteristics (matrix and/or nail bed alterations) were included to calculate the Nail Psoriasis Severity Index (NAPSI) score. Improvement degree was based on NAPSI score reduction. All patients were treated with roflumilast 0.3% cream daily for at least 16 weeks.Results
The case series included 7 patients with NP not associated with PsA. The mean baseline NAPSI score was 19, which decreased to 6.8 after 16 weeks of topical treatment. Roflumilast 0.3% cream was used both as monotherapy and/or in combination with topical steroids or acitretin. Interestingly, all patients reported quality of life improvements, and complete lesion clearance was achieved in almost all patients.Conclusions
Topical roflumilast showed promising results to treat topically NP. In this case series topical roflumilast was effective, well-tolerated and not associated with AEs.Weiterlesen
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Biologics effectively improve psoriatic skin lesions, but their impact on itch relief remains unclear.Objective
To evaluate itch improvement in severe psoriasis patients treated with ustekinumab or guselkumab.Methods
This retrospective study analyzed patients with severe psoriasis who completed initial efficacy evaluations after treatment with either biologic. Itch severity was assessed using numerical rating scale (NRS), visual analog scale, and verbal rating scale. NRS improvement was evaluated after three injections.Results
Among 108 patients (74 on ustekinumab, 34 on guselkumab), 77 (71.3%) had moderate-to-severe itch (NRS ≥4) at baseline. Of these, 63 (81.8%) achieved an NRS improvement of ≥4 points. Ustekinumab showed greater itch relief compared to guselkumab in NRS (p=0.033). On the other hand, guselkumab showed more reduction for psoriatic skin lesions than ustekinumab in the Psoriasis Area and Severity Index (p=0.040). In the moderate-to-severe itch group, patients with large plaques experienced significantly greater improvement in NRS than those with small plaques (p=0.012).Conclusion
While guselkumab is generally preferred for psoriatic skin lesions, ustekinumab may provide superior itch relief.Weiterlesen
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This study aimed to evaluate the required test characteristics that a psoriatic arthritis (PsA) biomarker test would need to achieve to be considered cost-effective.Methods
We adapted an existing Markov model to compare a hypothetical biomarker with current practice. The model followed a patient cohort aged 45 years with moderate psoriasis (PsO) in which PsA was prevalent but unrecognized over a 40-year time horizon. Patients were assumed to be routinely seen at a dermatology clinic. In the current practice arm, patients with PsA were clinically detected. In the biomarker arm, a hypothetical test was assumed to be administered at baseline. Patients who screened positive would accept a combination of conventional disease-modifying antirheumatic drugs and targeted treatment to slow disease progression. Progression was modeled as linear changes in Health Assessment Questionnaire (HAQ) scores. We varied the sensitivity, specificity, and biomarker price based on current development progress. Scenario analyses considered alternative patient cohorts with mild and severe PsO separately.Results
The base case showed that a biomarker test with 70 percent sensitivity, 80 percent specificity, and a price of US$500 would be cost-effective (incremental cost-effectiveness ratio US$47,566 per quality-adjusted life-year [QALY]). Three-way analyses showed that a test with 80 percent specificity could be cost-effective at a US$50,000 per QALY threshold with a sensitivity as low as 66 percent at US$500. Only a near-perfect test would be cost-effective at a US$1,000 price point. Results were sensitive to HAQ progression under treatment, therapy costs, and the patient population.Conclusion
This study supports the continued product development of candidate PsA biomarkers.Weiterlesen
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The management of moderate-to-severe psoriasis in patients with concurrent or previous malignancy presents a unique clinical challenge. Despite the transformative impact of biologic therapies on psoriasis treatment, the exclusion of patients with malignancy from clinical trials has led to a paucity of data regarding the safety and efficacy of systemic and biologic agents in this subgroup. Clinicians are thus often compelled to rely on registry data, real-world evidence, and expert opinion when navigating these complex cases.Objectives
To investigate prescribing practices among psoriasis experts for systemic and biologic therapies in patients with severe psoriasis and concomitant malignancy. The study aimed to elucidate trends in decision-making, perceptions of treatment risks, and adherence to multidisciplinary approaches.Methods
An electronic survey was disseminated to 141 members of the International Psoriasis Council (IPC) between December 2023 and June 2024. The self-administered questionnaire examined respondents' demographics, guideline familiarity, and preferences for systemic and biologic therapies across five malignancy types (breast cancer, melanoma, prostate cancer, lymphoma, and metastatic renal cell carcinoma) at varying remission intervals. Data were analysed descriptively.Results
Fifty-seven IPC councillors completed the survey (40%). Anti-IL-17 agents were the most commonly selected therapies across all malignancy scenarios for patients in remission, reflecting growing confidence in their safety profiles. For active malignancies, apremilast was the most frequently chosen agent, particularly for breast cancer (61%), melanoma (56%), and metastatic renal cell carcinoma (49%). Tumour necrosis factor-alpha (TNF-α) inhibitors and fumaric acid esters were the least frequently selected treatments for active malignancies. The majority of respondents (70%) believed current guidelines lacked clarity on treating psoriasis in the context of malignancy. Nearly half (49%) reported always consulting oncology teams before initiating systemic therapy for patients with recent malignancy diagnoses, underscoring the importance of a multidisciplinary approach.Conclusions
This study highlights significant variability in prescribing practices and a strong preference for biologics such as anti-IL-17 agents and apremilast. The findings underscore the urgent need for malignancy-specific guidelines informed by robust long-term safety data to support optimal decision-making and improve patient outcomes.Weiterlesen
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