JID innovations : skin science from molecules to population health最新文献

{"title":"Coencapsulation of Immunosuppressive Drug with Anti-Inflammatory Molecule in Pickering Emulsions as an Innovative Therapeutic Approach for Inflammatory Dermatoses","authors":"Maxime Sintès ,&nbsp;Petra Kovjenic ,&nbsp;Liasmine Haine (Hablal) ,&nbsp;Kevin Serror ,&nbsp;Mohamed Beladjine ,&nbsp;Véronique Parietti (Montcuquet) ,&nbsp;Marine Delagrange ,&nbsp;Bertrand Ducos ,&nbsp;Jean-David Bouaziz ,&nbsp;David Boccara ,&nbsp;Maurice Mimoun ,&nbsp;Armand Bensussan ,&nbsp;Martine Bagot ,&nbsp;Nicolas Huang ,&nbsp;Laurence Michel","doi":"10.1016/j.xjidi.2024.100273","DOIUrl":"10.1016/j.xjidi.2024.100273","url":null,"abstract":"<div><p>Psoriasis is an inflammatory skin disease characterized by epidermal and immune dysfunctions. Although efficient, current topical treatments display adverse effects, including skin atrophy and burning sensation, leading to poor patient adherence. To overcome these downsides, pickering emulsions were formulated in which the calcitriol-containing dispersed phase was stabilized with either cyclosporin A– or tacrolimus-loaded poly(lactic-co-glycolic) acid nanoparticles. This study aimed to investigate their biological effects on lymphocytes and epidermal cells and their effectiveness in an imiquimod-induced psoriasis-like mouse model. Results showed that both emulsions significantly inhibited nuclear factor of activated T cell translocation in T lymphocytes as well as their IL-2 production, cell activation, and proliferation. In keratinocytes, inhibition of nuclear factor of activated T cell translocation decreased the production of IL-8 and TNF-α. Topical application of emulsions over skin biopsies ex vivo showed accumulation of rhodamin B–coupled poly(lactic-co-glycolic) acid nanoparticles throughout the epidermis by immunofluorescence and significantly decreased the antigen-presenting capacity of Langerhans cells in relation to a reduced expression of activation markers CD40, CD86, and HLA-DR. Using an imiquimod-induced psoriasis model in vivo, pickering emulsions significantly alleviated psoriasiform lesions potentially attributed to the decreased cutaneous expression of T-cell markers, proinflammatory cytokines, chemokines, and specific epidermal cell genes. Altogether, pickering emulsion might be a very efficient formulation for treating inflammatory dermatoses.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100273"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000201/pdfft?md5=5840a5e889e492fcc62f06d177b01f94&pid=1-s2.0-S2667026724000201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140403255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Image Quality Assessment Using Convolutional Neural Network in Clinical Skin Images","authors":"Hyeon Ki Jeong ,&nbsp;Christine Park ,&nbsp;Simon W. Jiang ,&nbsp;Matilda Nicholas ,&nbsp;Suephy Chen ,&nbsp;Ricardo Henao ,&nbsp;Meenal Kheterpal","doi":"10.1016/j.xjidi.2024.100285","DOIUrl":"https://doi.org/10.1016/j.xjidi.2024.100285","url":null,"abstract":"<div><p>The image quality received for clinical evaluation is often suboptimal. The goal is to develop an image quality analysis tool to assess patient- and primary care physician–derived images using deep learning model. Dataset included patient- and primary care physician–derived images from August 21, 2018 to June 30, 2022 with 4 unique quality labels. VGG16 model was fine tuned with input data, and optimal threshold was determined by Youden’s index. Ordinal labels were transformed to binary labels using a majority vote because model distinguishes between 2 categories (good vs bad). At a threshold of 0.587, area under the curve for the test set was 0.885 (95% confidence interval = 0.838–0.933); sensitivity, specificity, positive predictive value, and negative predictive value were 0.829, 0.784, 0.906, and 0.645, respectively. Independent validation of 300 additional images (from patients and primary care physicians) demonstrated area under the curve of 0.864 (95% confidence interval = 0.818–0.909) and area under the curve of 0.902 (95% confidence interval = 0.85–0.95), respectively. The sensitivity, specificity, positive predictive value, and negative predictive value for the 300 images were 0.827, 0.800, 0.959, and 0.450, respectively. We demonstrate a practical approach improving the image quality for clinical workflow. Although users may have to capture additional images, this is offset by the improved workload and efficiency for clinical teams.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 4","pages":"Article 100285"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000328/pdfft?md5=3096c45a51c4538d05749966b424a85b&pid=1-s2.0-S2667026724000328-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141486565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Reconstructed Human Epidermis in a Chemically-Defined, Animal Origin-Free Cell Culture","authors":"Julia Bajsert ,&nbsp;Valérie De Glas ,&nbsp;Emilie Faway ,&nbsp;Catherine Lambert de Rouvroit ,&nbsp;Miguel Pérez-Aso ,&nbsp;Paul W. Cook ,&nbsp;Yves Poumay","doi":"10.1016/j.xjidi.2024.100298","DOIUrl":"10.1016/j.xjidi.2024.100298","url":null,"abstract":"<div><p>The Reconstructed Human Epidermis (RHE) model derived from epidermal keratinocytes offers an ethical and scientific alternative to animal experimentation, particularly in cutaneous toxicology and dermatological research, where the elimination of animal cruelty is of paramount importance. Thus, we compared commercially available chemically defined animal origin-free (cdAOF) supplements, designed for regenerative medicine, to the widely utilized supplement (human keratinocyte growth supplement), which contains growth factors and bovine pituitary extract. Herein we present the extended characterization of RHE derived from newborn, adult, and immortalized N/telomerase reverse transcriptase keratinocytes under cdAOF conditions. Culture of RHE in the cdAOF media produced histological features that were similar to that produced using human keratinocyte growth supplement, with the exception that the basal keratinocytes were less cylindrical. Additionally, immunolocalization of involucrin in the basal layer and increased mRNA expression of several inflammatory-proliferative markers were observed under cdAOF conditions. In RHEs cultured in cdAOF media, expression and immunolocalization of other expected markers of keratinization were similar, while monitoring of barrier function (transepithelial electrical resistance) revealed results that were statistically equal to, or lower than those observed in RHE cultured in human keratinocyte growth supplement. Our study indicates that reconstruction of RHE was accomplished under cdAOF culture conditions and that further refinement could promote an expanded use beyond regenerative medicine, for in vitro toxicology applications.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100298"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000456/pdfft?md5=727f6880ad1ae8364d70328a593b5c15&pid=1-s2.0-S2667026724000456-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141951884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug Repurposing Using Molecular Network Analysis Identifies Jak as Targetable Driver in Necrobiosis Lipoidica","authors":"Alysia N. Hughes ,&nbsp;Xing Li ,&nbsp;Julia S. Lehman ,&nbsp;Steven A. Nelson ,&nbsp;David J. DiCaudo ,&nbsp;Rekha Mudappathi ,&nbsp;Angelina Hwang ,&nbsp;Jacob Kechter ,&nbsp;Mark R. Pittelkow ,&nbsp;Aaron R. Mangold ,&nbsp;Aleksandar Sekulic","doi":"10.1016/j.xjidi.2024.100296","DOIUrl":"10.1016/j.xjidi.2024.100296","url":null,"abstract":"<div><div>Drug repurposing is an attractive strategy for therapy development, particularly in rare diseases where traditional drug development approaches may be challenging owing to high cost and small numbers of patients. In this study, we used a drug identification and repurposing pipeline to identify candidate targetable drivers of disease and corresponding therapies through application of causal reasoning using a combination of open-access resources and transcriptomics data. We optimized our approach on psoriasis as a disease model, demonstrating the ability to identify known and, to date, unrecognized molecular drivers of psoriasis and link them to current and emerging therapies. Application of our approach to a cohort of tissue samples of necrobiosis lipoidica (an unrelated; rare; and, to date, molecularly poorly characterized cutaneous inflammatory disorder) identified a unique set of upstream regulators, particularly highlighting the role of IFNG and the Jak–signal transducer and activator of transcription pathway as a likely driver of disease pathogenesis and linked it to Jak inhibitors as potential therapy. Analysis of an independent cohort of necrobiosis lipoidica samples validated these findings, with the overall agreement of drug-matched upstream regulators above 96%. These data highlight the utility of our approach in rare diseases and offer an opportunity for drug discovery in other rare diseases in dermatology and beyond.</div></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 6","pages":"Article 100296"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Pharmacodynamic Effects on Psoriatic Biomarkers by Guselkumab Versus Secukinumab Correlate with Long-Term Efficacy: An ECLIPSE Substudy","authors":"Andrew Blauvelt ,&nbsp;Yanqing Chen ,&nbsp;Patrick J. Branigan ,&nbsp;Xuejun Liu ,&nbsp;Samuel DePrimo ,&nbsp;Brice E. Keyes ,&nbsp;Monica Leung ,&nbsp;Steven Fakharzadeh ,&nbsp;Ya-Wen Yang ,&nbsp;Ernesto J. Muñoz-Elías ,&nbsp;James G. Krueger ,&nbsp;Richard G. Langley","doi":"10.1016/j.xjidi.2024.100297","DOIUrl":"10.1016/j.xjidi.2024.100297","url":null,"abstract":"<div><p>IL-23 is a cytokine produced by myeloid cells that drives the T helper 17 pathway and plays an essential role in the pathophysiology of plaque psoriasis. IL-23 activation initiates a cascade of cytokines subsequently inducing the expression of many psoriasis-related proteins. This study aimed to better understand the underlying mechanisms driving the differences between IL-23 and IL-17A blockade in patients with psoriasis and their implications for durability of clinical responses. Serum and/or skin biopsies were isolated from patients treated with guselkumab or secukinumab for evaluation of potential biomarkers of pharmacodynamic response to treatment. Guselkumab treatment led to significantly greater reductions of IL-17F and IL-22 serum levels than treatment with secukinumab at weeks 24 and 48, demonstrating sustained regulation of the IL-23/T helper 17 pathway. Analyses of proteomic and transcriptomic profiles of patient sera and skin biopsies demonstrated differential regulation of proteins involved in chemokine, TNF, and relevant immune signaling pathways to a greater degree with guselkumab than with secukinumab treatment. These data provide insights into the differences between the mechanisms and impact of IL-23 and IL-17A blockade in psoriasis, with implications for efficacy observations and treatment paradigms. Trial Registration: The original study was registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT03090100).</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100297"},"PeriodicalIF":0.0,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000444/pdfft?md5=01db74f44a90f4fcecc903affcff3cfb&pid=1-s2.0-S2667026724000444-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141979729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and Impact of Unacceptable Symptom State among Patients with Psoriatic Arthritis: Results from the National Psoriasis Foundation’s 2019 Annual Survey","authors":"","doi":"10.1016/j.xjidi.2024.100292","DOIUrl":"10.1016/j.xjidi.2024.100292","url":null,"abstract":"<div><p>The National Psoriasis Foundation surveyed a random, stratified sample of individuals with psoriatic disease in the United States to determine the prevalence of an unacceptable psoriatic arthritis (PsA) symptom state and its effect on depression and social participation. Acceptable and unacceptable levels of PsA were defined using established cutoff points (acceptable ≤4 vs unacceptable &gt;4) on the Psoriatic Arthritis Impact of Disease 9. Psoriasis severity was defined by body surface area: mild &lt; 3%, moderate–severe ≥ 3%. Depression was assessed utilizing the Patient Health Questionnaire 2. Social participation was assessed by the Patient Reported Outcome Information Measurement System Ability to Participate in Social Role and Activities-SF4a. The analysis cohort comprised 801 patients with PsA. Unacceptable disease activity level (Psoriatic Arthritis Impact of Disease &gt;4) was reported by 59.6% of participants. After adjusting for age, sex, and psoriasis severity, individuals with likely depression (OR = 0.014, <em>P</em> &lt; .001) and those with limited ability to participate in social roles and activities (OR = 0.05, <em>P</em> &lt; .001) were less likely to experience acceptable levels of PsA activity. Ultimately, the results demonstrated that most United States patients with PsA have unacceptable levels of disease activity, which is associated with increased prevalence of depression and limitations in social participation.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100292"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000390/pdfft?md5=848c12c7c5d789c8a2cbee55d431a42a&pid=1-s2.0-S2667026724000390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141400361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma","authors":"","doi":"10.1016/j.xjidi.2024.100288","DOIUrl":"10.1016/j.xjidi.2024.100288","url":null,"abstract":"<div><p>Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling–associated genes revealed elevated <em>PTCH1</em>, <em>HEY2</em>, <em>LGR6</em>, <em>FZD2</em>, <em>LEF1</em>, <em>ALCAM</em>, and <em>RUNX1</em> expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100288"},"PeriodicalIF":0.0,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000353/pdfft?md5=8e38d3493d42fc9fadec23a5fb353a36&pid=1-s2.0-S2667026724000353-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141405897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metastatic Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patient: A Systematic Review","authors":"","doi":"10.1016/j.xjidi.2024.100294","DOIUrl":"10.1016/j.xjidi.2024.100294","url":null,"abstract":"<div><p>Patients who are immunosuppressed, such as solid organ transplant recipients (SOTRs), are at a higher risk of developing cutaneous squamous cell carcinoma (cSCC). This population is at a higher risk of metastasis and worse disease-specific survival. The objective of this review is to better characterize the immunosuppressed population with metastatic cSCC. A literature search was conducted to identify reports of lymphatic metastases in immunosuppressed patients with cSCC. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed during creation of a cohort with desired inclusion and exclusion criteria. One hundred and thirty-five articles met the inclusion/exclusion criteria, yielding 1020 total cases. We discovered that the most common forms of immunosuppression within the cohort were solid organ transplantation and hematologic malignancy. White males and cSCC tumors involving the head and neck comprised most cases. Using Brigham and Women’s Hospital and Eighth edition of American Joint Committee on Cancer tumor staging criteria, we observed a trend toward higher stage tumors in SOTR than in patients with hematologic malignancy. This review confirms that known clinical risk factors for metastatic cSCC appear to be similar among the immunosuppressed population and the cSCC population at large. Interestingly, our data suggest that current staging systems may not accurately reflect metastatic risk among patients with hematologic malignancy.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100294"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000419/pdfft?md5=69c95570f1b3b57d39721c9bab2639e4&pid=1-s2.0-S2667026724000419-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141397624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of the Neurotrophin Network in Skin Squamous Cell Cancer and the Novel Use of the Zebrafish System","authors":"Marika Quadri ,&nbsp;Elisabetta Palazzo","doi":"10.1016/j.xjidi.2024.100295","DOIUrl":"10.1016/j.xjidi.2024.100295","url":null,"abstract":"<div><p>Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer. An increasing number of cSCCs are associated with dysregulation of key molecules that control skin homeostasis. These observations have increased interest in the role of neurotrophins and their receptors in the pathogenesis of cSCC. They have been demonstrated to have a considerable impact on the aggressiveness potential of skin cancer by both in vitro and in vivo models. In this context, mouse models are classically used to dissect proliferation versus differentiation balance, but they have some limitations in terms of time, space, and costs. Recently, zebrafish models have been implemented as a new tool to obtain information regarding the invasive capacity and metastasis of neoplastic cells. By xenotransplantation technique, cSCC cells from a patient’s biopsy or cell line can be successfully characterized, with or without the presence of genetic manipulation or treatments. In addition, the evaluation of the immune microenvironment contributes to potentially identifying connections and homologies with humans. In this review, we retrace the role of the neurotrophin network in healthy and pathological skin, particularly in cSCC. We review how zebrafish models can be important tools for studying cSCC development, growth, and potential treatments.</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100295"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000420/pdfft?md5=d8e7142288443c85db28eaed341b2084&pid=1-s2.0-S2667026724000420-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guselkumab Reduces Disease- and Mechanism-Related Biomarkers More Than Adalimumab in Patients with Psoriasis: A VOYAGE 1 Substudy","authors":"","doi":"10.1016/j.xjidi.2024.100287","DOIUrl":"10.1016/j.xjidi.2024.100287","url":null,"abstract":"<div><h3>Background</h3><p>Psoriasis is an immune-mediated inflammatory disease characterized by activation of IL-23–driven IL-17–producing T cell and other IL-23 receptor–positive IL-17–producing cell responses. Selective blockade of IL-23p19 with guselkumab was superior to blockade of TNF-α with adalimumab (ADA) in treating moderate-to-severe psoriasis. Objective: Pharmacodynamic responses of guselkumab versus ADA were compared in patients with psoriasis in VOYAGE 1.</p></div><div><h3>Design</h3><p>Inflammatory cytokine serum levels were assessed (n = 118), and lesional and nonlesional skin biopsies were collected (n = 38) in patient subsets at baseline and 4, 24, and 48 weeks after treatment to evaluate pharmacodynamic responses of guselkumab versus those of ADA.</p></div><div><h3>Results</h3><p>Guselkumab provided rapid reductions in serum IL-17A, IL-17F, and IL-22 levels by week 4 versus at baseline, which were maintained through weeks 24 and 48 (<em>P</em> &lt; .001). The magnitude of reduction of IL-17A and IL-22 at week 48 and IL-17F at weeks 4, 24, and 48 were greater with guselkumab than with ADA (all <em>P</em> &lt; .05). In the skin, guselkumab reduced the expression of IL-23/IL-17 pathway–associated and psoriasis-associated genes.</p></div><div><h3>Conclusion</h3><p>These data provide extensive characterization of pharmacodynamic anti-inflammatory responses to IL-23p19 and TNF-α inhibition in human blood and tissue over time with FDA-approved doses of guselkumab and ADA. <strong>Trial registration:</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span><span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT02207231).</p></div>","PeriodicalId":73548,"journal":{"name":"JID innovations : skin science from molecules to population health","volume":"4 5","pages":"Article 100287"},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667026724000341/pdfft?md5=e41b338ba36749e6935747be01c4f97d&pid=1-s2.0-S2667026724000341-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141414560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}