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Selection processes, transportability, and failure time analysis in life history studies
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Biostatistics. 2024 Oct 27:kxae039. doi: 10.1093/biostatistics/kxae039. Online ahead of print. ABSTRACT In life history analysis of data from cohort studies, it is important to address the process by which participants are identified and selected. Many health studies select or enrol individuals based on whether they have experienced certain health related events, for example, disease diagnosis or some complication from disease. Standard methods of analysis rely on assumptions concerning the independence of selection and a person's prospective life history process, given their prior history. Violations of such assumptions are common, however, and can bias estimation of process features. This has implications for the internal and external validity of cohort studies, and for the transportabilty of results to a population. In this paper, we study failure time analysis by proposing a joint model for the cohort selection process and the failure process of interest. This allows us to address both independence assumptions and the transportability of study results. It is shown that transportability cannot be guaranteed in the absence of auxiliary information on the population. Conditions that produce dependent selection and types of auxiliary data are discussed and illustrated in numerical studies. The proposed framework is applied to a study of the risk of psoriatic arthritis in persons with psoriasis. PMID:39462279 | DOI:10.1093/biostatistics/kxae039 Den ganzen Artikel lesen -
Effectiveness of tildrakizumab 200 mg: an Italian multicenter study
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J Dermatolog Treat. 2024 Dec;35(1):2420825. doi: 10.1080/09546634.2024.2420825. Epub 2024 Oct 27. ABSTRACT Introduction: Psoriasis is a chronic immune-mediated disease that can be challenging to treat, especially in patients with severe disease or high body weight. Tildrakizumab is a monoclonal antibody which inhibits IL-23, approved for moderate-to-severe psoriasis with a standard 100 mg dose. A 200 mg dose may provide greater efficacy for patients over 90 kg or with high disease burden. Methods: This multicenter, prospective study evaluated the effectiveness and safety of tildrakizumab 200 mg in patients with moderate-to-severe psoriasis, focusing on those with specific challenges: body weight over 90 kg, baseline PASI ≥20, and difficult-to-treat areas. The study also compared bio-naive versus bio-experienced and male versus female patients. Adults received tildrakizumab 200 mg subcutaneously at weeks 0 and 4, then every 12 weeks. Results: Clinical improvements were assessed using PASI, DLQI, genital PASI, and NAPSI scores. After 24 weeks, the mean PASI score dropped from 14.6 to 0.4, with PASI 90 and PASI 100 scores exceeding 80% (100.0% and 80.3%, respectively). DLQI scores improved from 14.2 to 1.8, and significant improvements were seen in genital PASI and NAPSI scores. No significant adverse events occurred. Conclusions: Tildrakizumab 200 has been shown to be an effective therapeutic option, particularly for patients with high body weight, significant disease burden, and involvement of sensitive areas with no new safety signals. PMID:39462515 | DOI:10.1080/09546634.2024.2420825 Den ganzen Artikel lesen -
Global Trends and Scientific Impact of Topical Probiotics in Dermatological Treatment and Skincare
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Microorganisms. 2024 Oct 3;12(10):2010. doi: 10.3390/microorganisms12102010. ABSTRACT The skin plays a crucial role in maintaining homeostasis and protecting against external aggressors. Recent research has highlighted the potential of probiotics and postbiotics in dermatological treatments and skincare. These beneficial microorganisms interact with the skin microbiota, modulate the immune response, and enhance the skin barrier, offering a promising therapeutic avenue for various skin conditions, such as acne, dermatitis, eczema, and psoriasis. This bibliometric study aims to analyze the global trends and scientific impact of topical probiotics in dermatology. By reviewing 106 articles published between 2013 and 2023, the study categorizes the applications of probiotics in wound healing, inflammatory skin diseases, and general skincare. The findings indicate a significant increase in publications from 2021 onwards, attributed to the heightened focus on medical research during the COVID-19 pandemic. This study also identifies the most productive countries, institutions, and authors in this field, highlighting the importance of international collaborations. The results underscore the efficacy of probiotic-based topical formulations in improving skin health, reducing inflammation, and enhancing wound healing. This comprehensive analysis supports the development of new therapeutic strategies based on topical probiotics and encourages high-quality research in this promising area. PMID:39458319 | PMC:PMC11510400 | DOI:10.3390/microorganisms12102010 Den ganzen Artikel lesen -
Lipid-Based Formulation of Baricitinib for the Topical Treatment of Psoriasis
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Pharmaceutics. 2024 Sep 30;16(10):1287. doi: 10.3390/pharmaceutics16101287. ABSTRACT BACKGROUND: Baricitinib, commonly used for autoimmune diseases, is typically administered orally, which can lead to systemic adverse effects. A topical formulation could potentially offer localized therapeutic effects while minimizing these side effects. OBJECTIVES: This study focuses on developing a lipid-based topical formulation of baricitinib (BCT-OS) for treating psoriasis. METHODS: The optimized formulation was then assessed for physical, chemical, and biopharmaceutical characterization. Furthermore, the anti-inflammatory efficacy of the formulation was tested in a model of psoriasis induced by imiquimod in mice, and its tolerance was determined by the evaluation of biomechanical skin properties and an inflammation test model induced by xylol in mice. RESULTS: BCT-OS presented appropriate characteristics for skin administration in terms of pH, rheology, extensibility, and stability. The formulation also demonstrated a notable reduction in skin inflammation in the mouse model, and high tolerability without affecting the skin integrity. CONCLUSIONS: BCT-OS shows promise as an alternative treatment for psoriasis, offering localized therapeutic benefits with a potentially improved safety profile compared to systemic administration. PMID:39458616 | PMC:PMC11510483 | DOI:10.3390/pharmaceutics16101287 Den ganzen Artikel lesen -
Model-Informed Precision Dosing for Personalized Ustekinumab Treatment in Plaque Psoriasis
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Pharmaceutics. 2024 Oct 4;16(10):1295. doi: 10.3390/pharmaceutics16101295. ABSTRACT BACKGROUND/OBJECTIVES: Implementing model-informed precision dosing (MIPD) strategies guided by population pharmacokinetic/pharmacodynamic (PK/PD) models could enhance the management of inflammatory diseases such as psoriasis. However, the extent of individual experimental data gathered during MIPD significantly influences the uncertainty in estimating individual PK/PD parameters, affecting clinical dose selection decisions. METHODS: This study proposes a methodology to individualize ustekinumab (UTK) dosing strategies for 23 Spanish patients with moderate to severe chronic plaque psoriasis., considering the uncertainty of individual parameters within a population PK/PD model. RESULTS: An indirect response model from previous research was used to describe the PK/PD relationship between UTK serum concentrations and the Psoriasis Area and Severity Index (PASI) score. A maximum inhibition drug effect (Imax) model was selected, and a first-order remission constant rate of psoriatic skin lesion (kout = 0.016 d-1) was estimated. CONCLUSIONS: The MIPD approach predicted that 35% and 26% of the patients would need an optimized and intensified dosage regimen, respectively, compared to the regimen typically used in clinical practice. This analysis demonstrated its utility as a tool for selecting personalized UTK dosing regimens in clinical practice in order to optimize the probability of achieving targeted clinical outcomes in patients with psoriasis. PMID:39458624 | PMC:PMC11510411 | DOI:10.3390/pharmaceutics16101295 Den ganzen Artikel lesen -
Pharmaceutics. 2024 Oct 14;16(10):1329. doi: 10.3390/pharmaceutics16101329. ABSTRACT BACKGROUND: The treatment of psoriasis has made considerable progress with biologicals, including tumor necrosis factor inhibitors, and recently, monoclonal antibodies inhibiting directly interleukin (IL) 17, IL-23, or both IL-12/23. Newer biologicals are directed to the interleukin pathway and appear to improve complete or near-complete clearance. The newer biologicals have also been shown to have an excellent safety profile. However, despite experience with patients having confirmed the results obtained in clinical trials, there are still few data on using the newer biologicals. METHODS: The present active study aimed to prospectively evaluate safety profiles and persistence of some biologicals in a multicenter pharmacovigilance study, that enrolled 733 patients treated with a biologic drug in five Calabrian hospital units. Informative and treatment persistence evaluations with predictors for suspension and occurrence of adverse events (AEs) were executed. In particular, reasons for treatment discontinuation in our program take account of primary/secondary failure or development of an AE. RESULTS: AEs occurred in 187/733 patients and serious AEs (SAEs) were identified in 5/733 patients. An number of 182/733 patients showed a primary/secondary inefficacy. The AEs and SAEs were described with adalimumab, infliximab, and etanercept but not with abatacept, brodalumab, tildrakizumab, golinumab, ixekizumab, guselkumab, risankizumab, secukinumab, and ustekinumab. CONCLUSIONS: Our analysis, although limited by a small sample size and a short-term follow-up period, offers suitable data on commonly used biological agents and their safety, interruption rate, and the attendance of SAEs. Real-world studies should be carried out to evaluate other safety interests. PMID:39458658 | PMC:PMC11510662 | DOI:10.3390/pharmaceutics16101329 Den ganzen Artikel lesen
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Pharmaceuticals (Basel). 2024 Oct 16;17(10):1376. doi: 10.3390/ph17101376. ABSTRACT Background/Objectives: This study investigates the chemical composition, antioxidant, antibacterial, and hemolytic properties of ylang-ylang (Cananga odorata) essential oil, with a focus on its potential therapeutic applications for dermatological diseases and the importance of transforming such bioactive properties into a stable, safe, and effective formulation. Methods/Rsults: Essential oils were extracted from flowers harvested in northern Grande Comore using hydro distillation at three different distillation times to examine the impact on yield and quality. Gas chromatographic analysis identified a complex mixture of compounds, including linalool, geranyl acetate, and benzyl benzoate. Antioxidant activity was assessed using DPPH, FRAP, TAC, and beta-carotene bleaching inhibition assays, revealing significant radical scavenging capabilities, with DPPH IC50 varying between 1.57 and 3.5 mg/mL. Antibacterial activity was tested against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, showing promising inhibition zones and minimum inhibitory concentrations. Hemolytic tests indicated varying degrees of red blood cell damage, emphasizing the need for careful concentration management in therapeutic applications. Molecular docking studies highlighted potential therapeutic targets for dermatological conditions, identifying high binding affinities for specific compounds against proteins involved in acne, eczema, and psoriasis. Conclusions: This comprehensive analysis underscores the potential of ylang-ylang essential oil (YEOs) as a natural alternative for antimicrobial treatments and dermatological applications, with its success dependent on optimized extraction methods and precise formulation to reduce cytotoxic effects. A formulation approach is crucial to ensure controlled release, improve bioavailability, and minimize skin irritation. PMID:39459015 | PMC:PMC11510078 | DOI:10.3390/ph17101376 Den ganzen Artikel lesen
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Fast Clinical Response of Bimekizumab in Nail Psoriasis: A Retrospective Multicenter 36-Week Real-Life Study
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Pharmaceuticals (Basel). 2024 Oct 16;17(10):1378. doi: 10.3390/ph17101378. ABSTRACT (1) Background/Objectives: Nail psoriasis (NP) is a chronic and difficult-to-treat disease, which causes significant social stigma and impairs the patients' quality of life. Moreover, nail psoriasis is a true therapeutic challenge for clinicians. The presence of nail psoriasis can be part of a severe form of psoriasis and can have predictive value for the development of psoriatic arthritis. Our real-world-evidence multicenter study aims to evaluate the efficacy of bimekizumab in nail psoriasis. (2) Methods: A retrospective analysis of a multicenter observational study included 834 patients affected by moderate-to-severe psoriasis, in 33 Dermatologic Units in Italy, treated with bimekizumab from December 2022 to September 2023. Clinimetric assessments were based on Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Physician's Global Assessment of Fingernail Psoriasis (PGA-F) for the severity of nail psoriasis at 0, 12, 24, and 36 weeks. (3) Results: Psoriatic nail involvement was present in 27.95% of patients. The percentage of patients who achieved a complete clearance of NP in terms of PGA-F 0 was 31.7%, 57%, and 88.5% at week 4, 16, and 36, respectively. PASI 100 was achieved by 32.03% of patients at week 4, by 61.8% at week 16, and by 78.92% of patients at week 36. The mean baseline PASI was 16.24. The mean DLQI values for the entire group of patients at baseline, at week 4, at week 16, and at week 36 were 14.62, 3.02, 0.83, and 0.5, respectively. (4) Conclusions: Therapies that promote the healing of both the skin and nails in a short time can also ensure a lower risk of subsequently developing arthritis which is disabling over time. Bimekizumab proved to be particularly effective to treat NP, with a fast response in terms of complete clearance, with over 88.5% of patients free from NP after 36 weeks. The findings of our real-world study showed that patients with moderate-to-severe PsO and concomitant NP had significantly faster and more substantial improvements in NP up to 36 weeks with respect to previous research findings. Considering the rapid healing of the nail, the dual inhibition of IL17 A and F might have a great value in re-establishing the dysregulation of keratin 17 at the nail level. PMID:39459016 | PMC:PMC11510175 | DOI:10.3390/ph17101378 Den ganzen Artikel lesen -
The Contribution of the Skin Microbiome to Psoriasis Pathogenesis and Its Implications for Therapeutic Strategies
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Medicina (Kaunas). 2024 Oct 3;60(10):1619. doi: 10.3390/medicina60101619. ABSTRACT Psoriasis is a common chronic inflammatory skin disease, associated with significant morbidity and a considerable negative impact on the patients' quality of life. The complex pathogenesis of psoriasis is still incompletely understood. Genetic predisposition, environmental factors like smoking, alcohol consumption, psychological stress, consumption of certain drugs, and mechanical trauma, as well as specific immune dysfunctions, contribute to the onset of the disease. Mounting evidence indicate that skin dysbiosis plays a significant role in the development and exacerbation of psoriasis through loss of immune tolerance to commensal skin flora, an altered balance between Tregs and effector cells, and an excessive Th1 and Th17 polarization. While the implications of skin dysbiosis in psoriasis pathogenesis are only starting to be revealed, the progress in the characterization of the skin microbiome changes in psoriasis patients has opened a whole new avenue of research focusing on the modulation of the skin microbiome as an adjuvant treatment for psoriasis and as part of a long-term plan to prevent disease flares. The skin microbiome may also represent a valuable predictive marker of treatment response and may aid in the selection of the optimal personalized treatment. We present the current knowledge on the skin microbiome changes in psoriasis and the results of the studies that investigated the efficacy of the different skin microbiome modulation strategies in the management of psoriasis, and discuss the complex interaction between the host and skin commensal flora. PMID:39459406 | PMC:PMC11509136 | DOI:10.3390/medicina60101619 Den ganzen Artikel lesen -
State-of-the-Art in Skin Fluorescent Photography for Cosmetic and Skincare Research: From Molecular Spectra to AI Image Analysis
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Life (Basel). 2024 Oct 6;14(10):1271. doi: 10.3390/life14101271. ABSTRACT Autofluorescence is a remarkable property of human skin. It can be excited by UV and observed in the dark using special detection systems. The method of fluorescence photography (FP) is an effective non-invasive tool for skin assessment. It involves image capturing by a camera the emission of light quanta from fluorophore molecules in the skin. It serves as a useful tool for cosmetic and skincare research, especially for the detection of pathological skin states, like acne, psoriasis, etc. To the best of our knowledge, there is currently no comprehensive review that fully describes the application and physical principles of FP over the past five years. The current review covers various aspects of the skin FP method from its biophysical basis and the main fluorescent molecules of the skin to its potential applications and the principles of FP recording and analysis. We pay particular attention to recently reported works on the automatic analysis of FP based on artificial intelligence (AI). Thus, we argue that FP is a rapidly evolving technology with a wide range of potential applications. We propose potential directions of the development of this method, including new AI algorithms for the analysis and expanding the range of applications. PMID:39459571 | PMC:PMC11509763 | DOI:10.3390/life14101271 Den ganzen Artikel lesen -
Global Comparison of COVID-19 Vaccination Rates among Psoriasis Patients
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Life (Basel). 2024 Oct 13;14(10):1297. doi: 10.3390/life14101297. ABSTRACT (1) Background: The purpose of this study is to compare the rate of COVID-19 vaccination among psoriasis patients internationally and to correlate it with their treatment regimens. (2) Methods: We conducted a cross-sectional study from January 2021 to October 2022 among adults in the United States (US), Chile, China, Switzerland, and Singapore using the Global Healthcare Study on Psoriasis survey. (3) Results: A total of 310 psoriasis patients in the US (98), Chile (32), China (80), Switzerland (39), and Singapore (61) were surveyed. Of these, 248 patients (80.0%) were vaccinated at least once for COVID-19 (Chile: 100%, Singapore: 100%, US: 93.9%, Switzerland: 69.2%, China: 45.0%). Compared with other countries, patients in China were 89% less likely to report at least one COVID-19 vaccination (1 - 0.11 = 0.89; OR 0.11; 95% CI: 0.03-0.48), and patients in Switzerland were 80% less likely (1 - 0.20 = 0.80; OR 0.20; 95% CI: 0.05-0.79). Compared with patients on biologics, patients on topicals were 10.9 (95% CI: 2.1-56.6) times more likely to report at least one COVID-19 vaccination, and patients on oral systemics were 7.2 times more likely (95% CI: 1.6-31.6). (4) Conclusions: Country of residence and treatment regimen are associated with different COVID-19 vaccination rates in psoriasis patients. PMID:39459597 | PMC:PMC11509075 | DOI:10.3390/life14101297 Den ganzen Artikel lesen -
The Effect of Szigetvár Medicinal Water on HaCaT Cells Exposed to Dithranol
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Life (Basel). 2024 Oct 17;14(10):1318. doi: 10.3390/life14101318. ABSTRACT (1) Introduction: Topical dithranol is still commonly used today as an effective treatment for psoriasis. Dithranol treatment is often supplemented with balneotherapy, which has been shown to increase effectiveness and reduce side effects. The inorganic salts (sulfhide, selenium, zinc) are usually thought to be responsible for the effect. The antioxidant effect of the waters is thought to be behind the therapeutic effect, for which inorganic substances (sulfides, selenium, zinc) are thought to be responsible. The organic matter content of medicinal waters is also particularly important, as humic acids, which are often found in medicinal waters, have antioxidant effects. (2) Methods: In this short-term experiment, we aimed to test the possible protective effect of Szigetvár medicinal water and its organic matter isolate on HaCaT cells exposed to dithranol. Malondialdehyde levels were measured, and RT-qPCR was used to investigate the gene expression of selected cytokines relevant in the oxidative stress response (IL-6, IL-8, TNF-α, GM-CSF) and the expression of microRNA-21. (3) Results: Szigetvár medicinal water and the organic isolate prevented the increase in malondialdehyde levels caused by dithranol treatment. The cytokine gene expressions elevated by dithranol exposure were reduced by the treatment. (4) Conclusions: Szigetvár medicinal water and organic substances alone may have a protective effect on patients' healthy skin surfaces against dithranol damage. We also demonstrated that the organic compounds are also responsible for the protective effect. PMID:39459618 | PMC:PMC11509105 | DOI:10.3390/life14101318 Den ganzen Artikel lesen -
Arch Dermatol Res. 2024 Oct 26;316(10):717. doi: 10.1007/s00403-024-03465-4. ABSTRACT It has been reported that many people with psoriasis have been diagnosed with secondary IgA nephropathy (IgAN). However, the mechanisms behind the association between psoriasis and IgAN have not been well clarified. The connection between psoriasis and IgAN deserves deeper exploration. Mendelian randomization (MR) analysis would be employed to explore the link of causality between IgAN and psoriasis, psoriasis vulgaris, other and unspecified psoriasis, guttate psoriasis, and arthropathic psoriasis. Transcriptomic analyses were carried out against the Gene Expression Omnibus databases. We identified crosstalk genes through the analysis of Differentially expressed genes and weight gene co-expression network analysis. Functional annotations were enriched for these crosstalk genes. Subsequently, we established a protein-protein interaction network, and candidate genes would be discovered through the utilization of the MCODE and CytoHubba plug-in applications. Lastly, the predictive efficacy of these genes was examined via creating receiver operating characteristic curves. The MR analysis suggested that psoriasis vulgaris patients were at a higher risk for IgAN. [OR = 1.040, 95%CI (1.005,1.076), p = 0.026 < 0.05]. Additionally, arthropathic psoriasis may augment the incidence of IgAN [OR = 1.081, 95%CI (1.040-1.124), p < 0.01] in the European population. Through the analysis of DEGs and WGCNA, we identified 12 significant genes (NETO2, RRM2, SLAMF7, GBP1, KIF20A, CCL4, MMP1, IL1β, NDC80, CXCL9, C15orf48, GSTA3), which may be potential crosstalk genes between the two diseases. Then, the functional annotation results indicated that the crosstalk genes seemed primarily involved in immune and inflammatory responses. By establishing the PPI network, we further discovered that CXCL9, IL1β, CCL4, and MMP1 play a vital part in psoriasis and IgAN, and all have good diagnostic values. Our MR analysis provided evidence that genetic vulnerability to IgAN may be associated with an elevated risk of psoriasis vulgaris and arthropathic psoriasis respectively among Europeans. Doctors should be aware of these associations when patients with psoriasis present with renal dysfunction, especially those with psoriasis vulgaris and arthropathic psoriasis. Chronic inflammation, drug effects, and immunity may contribute to the generation and development of both diseases. IL1β, CXCL9, CCL4, and MMP1 may be core biomarkers for psoriasis and IgAN. PMID:39460798 | DOI:10.1007/s00403-024-03465-4 Den ganzen Artikel lesen
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Clinical features and effects of cyclosporine in the treatment of psoriasis: a systemic review and meta-analysis
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Arch Dermatol Res. 2024 Oct 26;316(10):705. doi: 10.1007/s00403-024-03425-y. ABSTRACT To systematically evaluate clinical features and effects of cyclosporine in the treatment of psoriasis. Databases including Web of Science, PubMed, The Cochrane Library, Embase, CNKI, Wan Fang, and VIP were electronically searched for studies on the use of cyclosporine in the treatment of psoriasis, from inception to March 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. A meta-analysis was then performed. A total of 12 randomised controlled trial (RCT) studies were included. Compared with the control group, there were statistically significant differences in the effective rate, recurrence rate, erythema regression time, pustular resolution time, fever resolution time, and Psoriasis Area Severity Index (PASI) score of cyclosporine in the treatment of psoriasis. Moreover, the sub-group analysis showed that the effective rate of patients aged less than 40 years was significantly higher than that of the control group and the recurrence rate was significantly lower than that of the control group. The effective rate of psoriasis patients without nail lesions was significantly higher than that of control group. The effective rate of cyclosporin was significantly higher than that of dexamethasone acetate. There was no significant change in pooled sensitivity and specificity after each study was excluded one by one, indicating the stability of the meta-analysis. Cyclosporine had a high effective rate and low recurrence rate in the treatment of psoriasis, but it still had similar rate of adverse reactions compared to other drugs. This study systematically evaluated the effect of cyclosporine in the treatment of psoriasis and provided reference for clinical practice. PMID:39460805 | DOI:10.1007/s00403-024-03425-y Den ganzen Artikel lesen -
Lancet. 2024 Oct 26;404(10463):1679-1692. doi: 10.1016/S0140-6736(24)01750-1. ABSTRACT Biological monoclonal antibody drugs inhibit overactive cytokine signalling that drives chronic inflammatory disease in different organ systems. In the last 10 years, interleukin (IL)-23 inhibitors have attained an important position in the treatment of psoriatic skin and joint disease as well as inflammatory bowel diseases. Addressing an upstream pathological mechanism shared between these disorders, this drug class has high efficacy rates and a durable response that extends dosing intervals up to 3 months. Pooled clinical trial data show objective disease improvement for more than 70% of patients with psoriasis and up to 50% of patients with inflammatory bowel disease. The first antibody inhibitor for IL-23A targeted a p40 subunit shared with IL-12. Subsequently, even greater improvement was established for inhibitors of the p19 protein unique to IL-23A. IL-23 p19 inhibitors elicit clinical response in both bio-naive and bio-exposed patients and show superiority to tumour necrosis factor α inhibitors in plaque psoriasis. Reported differences in efficacy between p19 inhibitors suggest that individual drug action might be modulated by antibody affinity. Although long-term safety data are accumulating, rates of serious adverse events and infections for interleukin (IL)-23 inhibitors are similar to the rates for placebo across approved indications. PMID:39461795 | DOI:10.1016/S0140-6736(24)01750-1 Den ganzen Artikel lesen
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J Clin Aesthet Dermatol. 2024 Oct;17(10):63-67. ABSTRACT OBJECTIVE: Tildrakizumab, an anti-interleukin-23 p19 monoclonal antibody, is approved for the treatment of adults with moderate-to-severe plaque psoriasis. Limited evidence is available regarding the effects of tildrakizumab on patient-reported symptoms and satisfaction. This report describes the secondary endpoints of patient-reported symptoms and treatment satisfaction over 64 weeks in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in a Phase IV, real-world study. METHODS: In this uncontrolled, open-label study (NCT03718299), patients received tildrakizumab 100 mg at baseline, Week (W)4, and every 12 weeks thereafter to W52, with the final assessment at W64. Patient-reported secondary endpoints included numerical rating scale (NRS) scores for itch, pain, and scaling, and treatment satisfaction measured by 3 rating scales (Treatment Satisfaction Questionnaire for Medication [TSQM], Tildrakizumab Overall Satisfaction, and Patient Happiness with Psoriasis Control instrument) through W64. RESULTS: Of the 55 patients enrolled, 45 were assessed at W64. Mean NRS scores for itch, pain, and scaling all decreased from baseline beginning as early as W4 with maintenance through W64 (P≤0.001). Treatment satisfaction was positive throughout treatment based on all 3 measures. Mean±SD TSQM domain scores increased from 59.5±17.0 at W4 to 79.5±20.1 at W64 for Effectiveness and from 72.7±18.6 to 81.9±20.5 for Global Satisfaction. LIMITATIONS: The study is small and lacks a comparator arm. CONCLUSION: Tildrakizumab treatment improved patient-reported symptoms in patients with moderate-to-severe plaque psoriasis in a real-world setting and was associated with high levels of treatment satisfaction over 64 weeks. PMID:39445319 | PMC:PMC11495160 Den ganzen Artikel lesen
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J Clin Aesthet Dermatol. 2024 Oct;17(10):19-22. ABSTRACT OBJECTIVE: We sought to correlate the time lag between psoriatic arthritis (PsA) symptom onset and diagnosis to the likelihood and severity of depression, social impairment, and disease impact on quality of life. METHODS: This cross-sectional study conducted by the National Psoriasis Foundation (NPF) surveyed individuals with PsA using patient-reported outcome measures. RESULTS: The analysis cohort comprised 2,196 patients with PsA. Likelihood of depression progressively increased when time between PsA symptom onset and diagnosis was beyond six months (28.6% <6 months; 29.6% 7-12 months; 38.1% 13-24 months; 35.4% >2 years; p<0.01). Individuals with more than six months delay reported increasingly higher rates of experiencing moderate limitation in social participation (22.9% <6 months; 29.2% 7-12 months; 34.0% 13-24 months; 35.3% >2 years; p<0.001). Unacceptable PsA symptom rates (PsAID score >4) increased with time between PsA symptom onset and diagnosis (74.7% <6 months; 76.4% 7-12 months; 80.8% 13-24 months; 81.6% >2 years; p<0.05). These relationships persisted in body mass index (BMI) and age adjusted models. LIMITATIONS: The study only includes participants who were active members of the NPF, and all data was self-reported. CONCLUSION: Our results demonstrate that delays between PsA symptom onset and diagnosis that are greater than six months lead to increased likelihoods of depression, social disengagement, and impaired quality of life, and that longer delays lead to increasingly worse outcomes in these domains. PMID:39445325 | PMC:PMC11495158 Den ganzen Artikel lesen
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J Clin Aesthet Dermatol. 2024 Oct;17(10):18. NO ABSTRACT PMID:39445327 | PMC:PMC11495167 Den ganzen Artikel lesen
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J Eur Acad Dermatol Venereol. 2024 Oct 24. doi: 10.1111/jdv.20400. Online ahead of print. NO ABSTRACT PMID:39445679 | DOI:10.1111/jdv.20400 Den ganzen Artikel lesen
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Arch Physiol Biochem. 2024 Oct 24:1-13. doi: 10.1080/13813455.2024.2407547. Online ahead of print. ABSTRACT CONTEXT: Insulin resistance and a disturbed lipid profile are common associations with type 2 diabetes mellitus (T2DM) and different skin diseases, particularly psoriasis (PsO). OBJECTIVES: We investigated potential therapeutic mechanisms of metformin in a murine animal model of psoriasiform lesions in T2DM. MATERIALS AND METHODS: Forty-two rats were randomly divided into control, PsO, and type II DM (T2DM) groups. After confirmation of DM, the type II diabetic rats were allocated into T2DM+ PsO, T2DM+ PsO+ systemic metformin (S. met), T2DM+ PsO+ topical metformin (T. met)), and T2DM+ PsO + combined metformin (C. met). PsO was induced by topical imiquimod. RESULTS: Systemic administration of the cornerstone antidiabetic drug, metformin, was able to improve insulin resistance and lipid profile. At molecular levels, both topical and systemic metformin significantly increased AMP-activated protein kinase (AMPK), and lowered keratinocyte growth factor (KGF) / "Signal transducer and activator of transcription" (STAT)3 protein levels, and the IL-17RA and IL-17RC gene expression. CONCLUSION: Although its glucose-controlling effect was not optimum, T.met gel served anti-psoriatic and anti-inflammatory effects. PMID:39446079 | DOI:10.1080/13813455.2024.2407547 Den ganzen Artikel lesen
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Br J Dermatol. 2024 Oct 23:ljae402. doi: 10.1093/bjd/ljae402. Online ahead of print. ABSTRACT BACKGROUND: ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers. OBJECTIVES: This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis. METHODS: Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies. RESULTS: At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups. CONCLUSIONS: These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP. PMID:39442018 | DOI:10.1093/bjd/ljae402 Den ganzen Artikel lesen
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A novel metric of autoimmune disease burden and its estimated incidence across different stages in life cycle of women
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Autoimmun Rev. 2024 Oct 21:103671. doi: 10.1016/j.autrev.2024.103671. Online ahead of print. ABSTRACT AIM: To produce a unique metric 'autoimmune disease (ADs)' based on various single autoimmune disorder and estimate its case number and age-standardized rate of incidence for each stage in life cycle of women from 1990 to 2019, and to further explore their temporal trends at global, regional, and national levels. METHODS: A comprehensive classification for life cycle of women was proposed. The estimates and 95 % uncertainty intervals (UIs) for case number and rate of incidence for rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis, and type 1 diabetes mellitus in all age groups (< 1, 1-4, 5-9, 10-14, 15-19, 20-24, 25-29, ……,80-84, 85-89, 90-94, 95+) were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. 'ADs' was defined by combining these five disorders. Age standardization by direct method was utilized to estimate the age-standardized rate (ASR) of incidence of 'ADs' for each stage in life cycle of women. Joinpoint regression analysis was adopted to investigate temporal trends of ASR from 1990 to 2019 by calculating annual percentage change (APC) and average APC (AAPC). Associations of incidence in 2019 and change in incidence from 1990 to 2019, with Socio-demographic Index (SDI) were also explored. RESULTS: In 2019, global ASR of incidence of 'ADs' in childhood, adolescence, adulthood, senility, women of childbearing age, perimenopause, menopause, and sex mature adults at the best reproductive age were 45.46 (95 % CI: 36.40 to 55.09), 59.97(95 % CI:46.62 to 75.30), 104.45 (95 % CI: 84.55 to 127.79), 129.58 (95 % CI: 105.18 to 157.68), 89.51 (95 % CI: 71.94 to 110.35), 130.92 (95 % CI: 106.98 to 158.16), 132.94 (95 % CI: 108.76 to 160.90) and 85.78 (95 % CI: 68.72 to 106.37), respectively. Regionally, although ASR in eight life stages differed from distinct geographical areas, the top three highest ASR all occurred in Western Europe, Australasia, and High-income North America. From 1990 to 2019, global ASR in childhood (AAPC: -0.39, [95 % CI: -0.4 to -0.38], p < 0.001), adolescence (AAPC: -0.4, [95 % CI: -0.41 to -0.4], p < 0.001), adulthood (AAPC: -0.53, [95 % CI: -0.55 to -0.51], p < 0.001), senility (AAPC: -0.4, [95 % CI: -0.41 to -0.38], p < 0.001), women of childbearing age (AAPC: -0.53, [95 % CI: -0.55 to -0.5], p < 0.001), perimenopause (AAPC: -0.56, [95 % CI: -0.59 to -0.52], p < 0.001), menopause (AAPC: -0.56, [95 % CI: -0.59 to -0.53], p < 0.001), and sex mature adults at the best reproductive age (AAPC: -0.5, [95 % CI: -0.51 to -0.49], p < 0.001) all significantly decreased. Nationally, ASR and its temporal trends in eight life stages varied significantly across 204 countries and territories. Additionally, incidence in 2019 and change in incidence from 1990 to 2019 were positively correlated with SDI across nations. CONCLUSIONS: Significant heterogeneities in incidence of autoimmune diseases across nations, with higher sociodemographic development level presenting higher burden, suggest that flexible health policy and targeted resource allocation tailored to sociodemographic status are crucial for each country. PMID:39442592 | DOI:10.1016/j.autrev.2024.103671 Den ganzen Artikel lesen -
Liver fibrosis in inflammatory arthritis patients treated with methotrexate and hydroxychloroquine: A FIB-4 index analysis
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Int J Rheum Dis. 2024 Oct;27(10):e15390. doi: 10.1111/1756-185X.15390. ABSTRACT OBJECTIVES: To evaluate the risk of liver fibrosis and associated factors with the non-invasive fibrosis score-4 (FIB-4) index in patients with inflammatory arthritis using methotrexate (MTX). METHODS: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who were followed up in the rheumatology outpatient clinic, who were on methotrexate only and for whom FIB-4 index was could be calculated at methotrexate initiation and follow-up were included. The FIB-4 index was calculated according to the following formula: age (years) × AST(IU/L)/(platelet count(10 (9)/L) × √ALT(IU/L)). The patients' demographics, comorbidities, other treatments, cumulative MTX dose, and reasons for MTX cessation were assessed. For the multivariate analysis, possible factors associated with intermediate-high risk FIB-4 index at last visit were determined. RESULTS: A total of 107 patients were enrolled in the study, of whom 82 (76.6%) had RA and 25 (23.4%) had PsA. At the initiation of MTX, 24 (22.4%) patients had intermediate-high risk FIB-4 index. Comorbidities and the rate of ≥3-4 Charlson comorbidity index were more common in patients with intermediate-high risk FIB-4 index. A total of 37 (34.5%) patients had intermediate-high risk FIB-4 index at the last visit after median 3.6 (0.3-22.06) years follow-up. The median cumulative MTX dose was 2550 mg (1050-13.991). Cumulative MTX dose [OR 1.18 (1.01-1.33), p = .03] and diabetes mellitus [OR 4.60 (1.74-12.50), p = .002] were associated factors with intermediate-high risk FIB-4 index. The concomitant use of hydroxychloroquine (HCQ) was found to be a low-risk factor for FIB-4 index [OR 0.28 (0.10-0.78) p = .015]. CONCLUSION: The FIB-4 index is a non-invasive method that can be used in daily rheumatology practice for the evaluation and follow-up of patients who will use methotrexate. Comorbidities and cumulative MTX dose seem to be related with the risk of liver fibrosis. Concomitant use of HCQ with MTX may reduce the risk of liver fibrosis. PMID:39439367 | DOI:10.1111/1756-185X.15390 Den ganzen Artikel lesen -
Insights Into the Epidemiological, Clinical, Histopathological, and Dermoscopic Aspects of Chronic Plaque Psoriasis
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Cureus. 2024 Sep 22;16(9):e69912. doi: 10.7759/cureus.69912. eCollection 2024 Sep. ABSTRACT Background Psoriasis is a persistent inflammatory condition of the skin marked by clearly demarcated red plaques adorned with silvery scales. It impacts individuals across different age ranges and presents with unique clinical, histological, and dermoscopic characteristics. This research seeks to offer an extensive assessment of the demographic, clinical, histological, and dermoscopic attributes of chronic plaque psoriasis (CPP). Methodology A total of 60 patients with CPP were included in this study. Data were collected on demographic characteristics, disease duration, clinical features, histopathological findings, and dermoscopic patterns. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York), employing descriptive statistics to summarize demographic and clinical characteristics and histopathological and dermoscopic findings. Results The study included 60 patients with CPP, predominantly aged 41-50 years (n=18, 30%), with a higher prevalence in males (n=35, 58.3%). Plaque psoriasis was the most common type observed (75%), with lesions primarily located on the scalp (n=30, 50%) and elbows (n=25, 41.7%), consistent with typical psoriasis distribution patterns. Histopathological analysis revealed acanthosis in 55 patients (91.7%) and parakeratosis in 50 patients (83.3%), indicating thickened epidermis and retention of nuclei in the stratum corneum, which are characteristic of psoriasis. Additionally, Munro's microabscesses were found in 30 patients (50%) and spongiform pustules in 10 patients (16.7%), supporting the diagnosis through classic markers. Dermoscopic evaluations identified red dots or globules in 55 patients (91.7%) and white scales in 50 patients (83.3%), essential for differentiating psoriasis from other skin conditions. Further dermoscopic findings included micro-erosions in 25 patients (41.7%), hemorrhagic spots in 15 patients (25%), and yellowish scales in 20 patients (33.3%), reflecting disease activity and inflammation. Conclusion This study underscores the importance of a multifaceted approach in diagnosing and managing CPP. The prevalence of psoriasis in middle-aged males and the common clinical presentation on the scalp and elbows are consistent with previous studies. Histopathological and dermoscopic features provide critical diagnostic support and can guide effective treatment strategies. Continued research is essential to enhance understanding and management of this prevalent dermatological condition. PMID:39439643 | PMC:PMC11495829 | DOI:10.7759/cureus.69912 Den ganzen Artikel lesen -
Case report: Intralesional secukinumab injection for pediatric nail psoriasis: does it have to be a positive outcome?
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Front Immunol. 2024 Oct 7;15:1435141. doi: 10.3389/fimmu.2024.1435141. eCollection 2024. ABSTRACT Recent studies have shown that local injection of secukinumab can achieve positive therapeutic effects when applied in the treatment of nail psoriasis. At present, there have been no other studies on the use of biological agents in the treatment of pediatric nail psoriasis. Three children were included in the study to evaluate the efficacy and safety of periungual injection and long-term injection of secukinumab in the treatment of nail psoriasis in children. It was found that local injection did not achieve a remarkable therapeutic effect. The nail lesions were improved continuously by subcutaneous injection once a month. PMID:39439789 | PMC:PMC11495258 | DOI:10.3389/fimmu.2024.1435141 Den ganzen Artikel lesen