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Bei Neurodermitis und Psoriasis spielt nicht nur das Immunsystem verrückt. Auch die Hautbewohner ändern sich. Forschende haben jetzt genauer auf Pilze und Bakterien geschaut. Vor allem die Hefepilze der Gattung Malassezia geraten aus dem Gleichgewicht. In entzündeter Haut sind die Pilze schlechter mit Bakterien vernetzt. Bei Neurodermitis nimmt eine Art namens Malassezia arunalokei ab, während der Problemkeim Staphylococcus aureus zunimmt. Das passt zu starken Entzündungszeichen mit dem Botenstoff IL 17. Bei Psoriasis hängen die Pilzänderungen mit IL 17 und mit Fettstoffwechsel in der Haut zusammen. Die Autoren hoffen, man kann das Hautmikrobiom später zur Einschätzung der Krankheitsaktivität und für neue Therapien nutzen. Originaltitel: Multi-omics analyses reveal host-microbe interactions in atopic dermatitis and psoriasis. Link zur Quelle

### Haut und Gelenke: Was die Studie für Euch bedeutet Die Übersichtsarbeit zeigt, wie eng Psoriasis und Psoriasis-Arthritis über eine Haut–Gelenk-Achse verbunden sind.[1][4] Entzündete Haut kann Immunzellen freisetzen, die in den Blutkreislauf und weiter in die Gelenke wandern.[1][4][14] Dort treffen sie auf Gelenkzellen und lösen Entzündungen aus.[1][7] Etwa ein Drittel der Menschen mit Psoriasis entwickelt eine Gelenkbeteiligung.[1][20] Die Forschenden suchen nach Merkmalen im Blut, in der Haut und im Gelenk, die früh zeigen, wer ein höheres Risiko hat.[2][11] Das kann helfen, Therapien gezielter auszuwählen.[2][5][17] Für Euch heißt das: Achtet auf neue Gelenk- oder Rückenschmerzen, Morgensteifigkeit und Schwellungen und sprecht früh mit Euren Ärztinnen und Ärzten.[20] Kontrollen von Haut, Nägeln und Gelenken sollten zusammen gedacht werden.[11][19] Wenn Ihr bereits eine Therapie bekommt, wird in Zukunft besser abschätzbar sein, ob sie eher auf Haut, Gelenke oder beides wirkt.[2][16] Originaltitel: From psoriatic plaque to synovium: decoding the skin–joint axis in psoriatic arthritis - Nature Reviews Rheumatology Link zur Quelle

Trial number: 2023-509216-28-00 Overall trial status: Ongoing, recruitment ended Trial title: EffisayilTM ON: An open-label, long term extension study to assess the safety and efficacy of spesolimab treatment in patients with Generalized Pustular Psoriasis (GPP) Medical conditions: Generalized Pustular Psoriasis Status in each country: France:Ongoing, recruitment ended, Italy:Ongoing, recruitment ended, Germany:Ongoing, recruitment ended, Belgium:Ongoing, recruitment ended, Spain:Ongoing, recruitment ended Trial phase: Therapeutic exploratory (Phase II) Therapeutic Areas: Diseases [C] - Skin and Connective Tissue Diseases [C17] Primary end point: Occurrence of treatment emergent adverse events (TEAEs) up to week 252 of maintenance treatment Secondary end point: The reoccurrence of a GPP flare defined by GPPGA, Time to first achievement of a GPPGA score of 0 or 1 in patients who received flare rescue treatment, A GPPGA pustulation sub-score of 0 indicating no visible pustules, by visit in patients who received flare rescue treatment, Change from baseline in Psoriasis Symptom Scale (PSS) score, by visit in patients who received flare rescue treatment Age of participants: 65+ years, 0-17 years, 18-64 years Gender of participants: Female, Male Trial region: In both EEA and non-EEA Planned number of participants: 25 Sponsor: Leo Pharma A/S Sponsor type: Pharmaceutical company Trial product: Spesolimab Results posted: No Overall decision date: 12/02/2024 Countries decision date: FR: 13/02/2024, DE: 13/02/2024, BE: 19/02/2024, ES: 12/02/2024, IT: 18/03/2024 Last updated date: 03/08/2026Den kompletten Artikel zeigen

Menschen mit Psoriasis und anderen entzündlichen Hautkrankheiten haben oft Probleme im Job. Die Übersicht fasste 196 Studien mit Erwachsenen zusammen. Am häufigsten ging es um Psoriasis und Neurodermitis. Die meisten Arbeiten untersuchten Produktivität im Beruf mit anerkannten Fragebögen. Die Ergebnisse zeigen, dass die Krankheiten nicht nur Leistung mindern sondern auch zu Burnout führen können und den Jobstatus gefährden. Für seltenere Krankheiten und für Länder mit wenig Geld gibt es fast keine Daten. Die Forschenden wollen klar sagen, wie stark die Arbeit leidet und Betroffene besser unterstützen. Originaltitel: Mapping the global work-related impact of immune-mediated inflammatory skin diseases: a systematic review. Link zur Quelle

https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-510759-37-00

### Was bedeutet diese Forschung zu Anthralin? Anthralin wird seit langem als Creme gegen Psoriasis eingesetzt.[1][3] Es bremst das schnelle Wachstum der Hautzellen und kann Plaques gut zurückbilden.[1][3] Die Studie zeigt: Die reizende Wirkung von Anthralin auf gesunde Haut aktiviert das Immunsystem sehr stark. In Tierversuchen lässt sich diese Wirkung nutzen, um über die Haut eine Art „Impfung“ zu verstärken, zum Beispiel gegen Krebszellen. Für Euch heißt das: Im Moment ändert sich an der Behandlung von Psoriasis nichts. Die Daten stammen aus Mausmodellen. Ob dieser Ansatz beim Menschen wirkt und sicher ist, muss erst geprüft werden. Positiv ist: Ein bekanntes Psoriasis‑Medikament bleibt in der Forschung wichtig. Das kann langfristig zu neuen Möglichkeiten führen, etwa wenn Menschen mit Psoriasis zusätzlich Krebs haben. Bis dahin gilt: Anthralin nur nach ärztlicher Anweisung nutzen. Eure Hautpflege und Euer Alltag müsst Ihr nicht anpassen. Originaltitel: Anthralin—From Psoriasis Drug to Power Adjuvant Link zur Quelle

Psoriasis is associated with an increased risk of major adverse cardiovascular events (MACE), and biologic therapy may reduce this risk by targeting systemic inflammation. However, limited data exist on whether long term MACE risk differs by biologic class or across racial groups. We conducted a retrospective cohort study to assess the risk of primary MACE in psoriasis patients receiving biological therapies, stratified by biological class, compared with biologic-naïve psoriasis patients. Whether MACE risk among biologic-treated patients varied by race was further examined. After 1:1 propensity score matching, 36 330 biologic-treated patients were compared with 36 330 non-biologic-treated patients. Incident MACE was assessed over 10 years. Class-specific analyses evaluated mutually exclusive biologic exposure groups, including TNF inhibitors (TNFi), IL-17 inhibitors (IL-17i), IL-12/23 inhibitors (IL-12/23i), and IL-23 inhibitors (IL-23i), each compared with an independently matched nonbiologic psoriasis comparator cohort. Race stratified analyses were restricted to biologic-treated patients, with White patients serving as the reference group. Psoriasis patients treated with biologics exhibited a 37% lower hazard of MACE compared with non-biologic users over the 10-year follow-up period [2160 vs. 3294; HR 0.63 (0.60-0.67)]. Class-specific analyses revealed reductions in MACE risk for TNFi [1403 vs. 1844; HR: 0.74 (0.69-0.80)], IL-17i [285 vs. 450; HR: 0.61 (0.53-0.72)], IL-12/23i [280 vs. 374; HR: 0.73 (0.62-0.86)], and IL-23i [238 vs. 363; HR: 0.64 (0.54-0.76)]. Race stratified analyses showed broadly similar MACE risk across racial groups; although, patients identifying as Non-White treated with TNFi did experience a reduced MACE risk compared to White patients [127 vs. 162; HR: 0.79 (0.62-0.99)]. This isolated finding should be interpreted cautiously given multiple race stratified comparisons. Overall, biologic therapy is associated with lower 10-year MACE risk among patients with psoriasis, with findings observed across biologic classes and largely consistent across racial strata.Weiterlesen

BackgroundTyrosine kinase 2 (TYK2), a key part of the inflammatory cascade responses, plays an integral role in the pathogenesis of psoriasis. Socrodeucitinib, an oral, TYK2 allosteric inhibitor, selectively inhibits TYK2 cytokine signalling pathways in psoriasis pathogenesis.ObjectivesTo evaluate the efficacy and safety of socrodeucitinib in patients with moderate-to-severe plaque psoriasis.MethodsIn this phase 2, double-blind, placebo-controlled trial, 125 patients were randomly assigned (1:1:1) to receive socrodeucitinib at 6 mg, 12 mg or placebo orally, once daily, for 12 weeks. The primary endpoint was the proportion of patients with a 75% or greater reduction from the baseline in the Psoriasis Area and Severity Index (PASI) score at week 12.ResultsAt week 12, significantly more patients treated with socrodeucitinib achieved a 75% reduction from baseline in PASI score compared with placebo (28.6% at 6 mg, 72.1% at 12 mg vs. 7.5% for placebo, p < 0.05 and p < 0.001, respectively). At the 12 mg dose, socrodeucitinib resulted in significantly higher response rates compared to placebo, with 46.5% of patients achieving PASI 90 (p < 0.001) and 11.6% achieving PASI 100 (p < 0.05). The treatment of socrodeucitinib also led to significantly higher proportions of patients achieving sPGA responses of 0 or 1 compared to placebo: 33.3% at 6 mg and 65.1% at 12 mg versus 10% for placebo (p < 0.05 and p < 0.001, respectively). Most common adverse events included upper respiratory tract infection which demonstrated a certain dose dependency. Most treatment-related adverse events were mild or moderate, and serious adverse events were infrequent, with no clinically meaningful abnormal trend in laboratory parameters.ConclusionsSocrodeucitinib demonstrated significantly greater clearing of psoriasis plaques compared to placebo in patients with moderate-to-severe plaque psoriasis and illustrated a favourable safety and tolerability profile, warranting further investigation in longer-duration and larger trials.Weiterlesen

IntroductionThe global burden of psoriatic arthritis (PsA) is considerable, with major effects on both quality of life and life expectancy. Despite the existence of a diverse array of therapeutic interventions, approximately 40-50% of patients do not achieve the established therapeutic targets. Challenges related to tolerance, compliance, and therapeutic escape persist.Areas coveredThis study is a comprehensive review of the current literature analyzing the central role of interleukin-17 (IL-17) in the pathogenesis of PsA and emphasizing current and investigational therapies for IL-17A blockade. A structured search was conducted in PubMed for the following terms investigational IL-17A antagonist and Psoriatic arthritis. We aimed for at least 100 research papers published within the last 20 years. In addition, clinical trials databases focusing on phase II - III IL-17A antagonists treatment in Psoriatic Arthritis were also reviewed.Expert opinionThe current stage of development and expansion of IL-17A antagonists encompasses the third generation of such molecules. This generation includes small, injectable molecules such as sonelokimab and izokibep; oral molecules; and bispecific monoclonal antibodies. This approach is purported to facilitate enhanced tissue diffusion, augmented efficacy in refractory forms, and simplified utilization. The future of PsA treatments is contingent upon the implementation of precision medicine, which leverages predictive biomarkers to personalize treatment from the moment of diagnosis. This could help control disease early and prevent progression, beyond the current Treat-to-Target strategy which mainly focuses on managing existing symptoms. The overarching objective is no longer to treat to target, but rather to treat to intercept, while ensuring the highest rate of control and tolerance for the patient.Weiterlesen

Psoriasis is an immune-mediated chronic inflammatory skin disease characterized by scaly plaques, erythema, and thick skin. Psoriasis management is complicated and multifaceted as this disease is linked to serious systemic consequences like infections, psoriatic arthritis, cardiovascular diseases, and psychological complications. In the current study, a mice model of psoriasis was established by topical application of 5% imiquimod (IMQ) cream on the shaved dorsal skin and left ear pinna of mice for 7 days. The animals in treatment groups were treated topically with different concentrations of clove oil (CO) (5, 10 and 20%), alone and in combination with flurbiprofen (FBR 5 and 10%), and betamethasone and salicylic acid combination (betasalic® ointment, a standard drug) for the next 7 days. Disease induction and treatment responses were assessed based on modified psoriasis area and severity index (modified PASI) score. On day 15, animals were euthanised, and blood and skin samples were collected for biochemical and histopathological analyses, along with a quantitative assessment of psoriasis-associated inflammatory gene expression using RT-qPCR techniques. Phytochemical tests were performed to detect total tannin, flavonoid, phenolic, and saponin contents of CO. CO 20% and FBR 5% combination and betasalic ointment treatments resulted in a significant (p < 0.05) reduction in erythema, scaling, and skin thickness with an overall modified PASI score of 4.5 ± 0.29 and 4.33 ± 0.33 when compared with the DC group (PASI score = 12 ± 00). Complete blood count analysis revealed a significant reduction (p < 0.05) in total leukocytes, neutrophils, and lymphocytes counts in the CO 20% and FBR 5% combination and betasalic ointment treated groups as compared with DC group. Moreover, a significant decrease in the spleen-to-body weight index (SBWI) was observed in the CO 20% and FBR 5% combination and betasalic ointment treated groups as compared with SBWI of DC group, highlighting the potential immune regulatory properties of CO and FBR. Histopathological analysis of skin tissues revealed a significant improvement in epidermal architecture and a reduction in inflammatory cells infiltration in the treated groups. RT-qPCR analysis revealed down-regulation in the mRNA expression of pro-inflammatory and oxidative stress-inducing genes. Phytochemical analyses confirmed the presence of flavonoids, tannins, phenolic compounds, and saponins in the CO. Overall, these findings suggest that the clove oil-flurbiprofen combination has the potential to reduce skin inflammatory conditions possibly via modulation of oxidative and inflammatory pathways.Weiterlesen

BackgroundDifficult-to-treat psoriatic arthritis (D2T PsA) represents a challenging condition characterized by inadequate response to multiple therapeutic agents. Real-world data on the effectiveness of Janus kinase inhibitors (JAKi) in this population remain limited.ObjectiveTo evaluate the effectiveness, safety, and treatment persistence of Upadacitinib (UPA) in patients with D2T PsA using both clinical and ultrasound assessments.Patients and methodsThis observational retrospective study included patients with PsA who failed at least one conventional DMARD and two biologic DMARDs with different mechanisms of action. All patients received UPA 15 mg once daily as monotherapy. Treatment persistence was assessed over 140 weeks, while effectiveness data were collected at four time points following baseline (12, 24, 48, and 104 weeks). Clinical measures included: PASI; cDAPSA score; swollen/tender joints count; assessment of enthesitis and dactylitis; VAS scores for disease activity/pain; HAQ. At baseline and during the follow-up, ultrasound imaging was performed according to the EULAR-OMERACT ultrasound score.ResultsTwenty-five patients were enrolled. After 140 weeks, treatment persistence was 68%. A rapid and sustained improvement in disease activity was observed, with mean cDAPSA decreasing from 27.88±5.2 at baseline to 12.04±8.17 at week 12 and 4.88±4.54 at week 52. At one year, 70.6% of patients achieved complete remission and 23.6% low disease activity. Ultrasound findings confirmed the clinical improvement, with a significant reduction in the EULAR-OMERACT score and complete resolution of enthesitis after one year of treatment. Most patients (94.1%) maintained complete remission or low disease activity up to week 104. Skin condition also improved significantly as demonstrated by the marked reduction in PASI score which decreased from a baseline value of 2.22 ± 2.62 to 0.21 ± 0.36 after 52 weeks of treatment. The safety profile was favorable, with mild lipid and CPK abnormalities being the most common adverse events.ConclusionIn this real-world cohort of patients with D2T PsA, UPA demonstrated sustained clinical and ultrasound effectiveness with a favorable safety profile and good long-term treatment persistence.Weiterlesen

Vitamin D (VD) is a secosteroid hormone with critical physiologic roles in calcium homeostasis and bone mineralization. Recently, studies have uncovered VD's broader effects on immune system and nervous system function. VD receptors (VDRs) and enzymes responsible for the metabolism of VD have been discovered in dorsal root ganglion (DRG) neurons and nociceptive sensory neurons, implicating VD as a potential regulator of neurogenic inflammation. Neurogenic inflammation is a phenomenon in which sensory nerve fibers in the peripheral nervous system (PNS) are activated and release neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), resulting in vasodilation, cytokine production, and immune cell infiltration. This process has been shown to drive chronic inflammatory skin disorders, including atopic dermatitis (AD) and psoriasis. VD has been recognized as a key factor in the pathogenesis and management of both conditions; however, the mechanism underlying its clinical benefits remains unclear. Emerging evidence has shown VD to influence CGRP signaling, interleukin-6 (IL-6) production, and TRPV1 channel activity-pathways that are integral to nociception and pruritus, as well as the Th17- and Th2-driven inflammation seen in psoriasis and AD, respectively. Thus, this review provides an overview of VD's possible mechanistic role in neurogenic skin inflammation and the implications of these pathways for identifying new therapeutic targets for psoriasis and AD.Weiterlesen

BackgroundIncreasing evidence shows that, compared with the general population, the prevalence of coronavirus disease 2019 is significantly higher in patients with psoriasis treated with immunosuppressive therapy. However, the underlying mechanisms have not yet been clarified.Materials and methodsThe aim of this study was to further investigate the molecular mechanisms underlying these two diseases. Gene expression profiles for coronavirus disease 2019 and psoriasis were downloaded from the gene expression omnibus database (GSE150316 and GSE30999). After identifying the common differentially expressed genes between coronavirus disease 2019 and psoriasis, functional annotation, protein-protein interaction network analysis, module construction, and hub gene identification were performed. Finally, transcription factor-gene regulatory and transcription factor-miRNA regulatory networks of the hub genes were constructed.ResultsA total of 306 common differentially expressed genes, including 168 upregulated genes and 138 downregulated genes, were identified and used for subsequent analysis. According to Kyoto Encyclopedia of Genes and Genomes enrichment analysis, the Rap1 signaling pathway, axon guidance, and focal adhesion contribute to the occurrence and development of coronavirus disease 2019 and psoriasis. Finally, five hub genes, namely EGF, IL1B, SERPINA1, CD8A, and WNT5A, were identified using the CytoHubba plug-in. Among them, three hub genes (EGF, SERPINA1, and CD8A) showed good diagnostic marker value for coronavirus disease 2019 and psoriasis.ConclusionOur findings suggest that coronavirus disease 2019 and psoriasis share common molecular mechanisms that are driven by several specific hub genes. This study provides new insights into the relationship between coronavirus disease 2019 and psoriasis.Weiterlesen

No abstract supplied.Weiterlesen

Systemic psoriasis treatment options have rapidly expanded in Japan, including the approval of tyrosine kinase 2 and interleukin-36 receptor inhibitors in 2022. However, contemporary real-world treatment patterns across plaque, erythrodermic, and generalized pustular psoriasis remain incompletely characterized. Using a Japanese hospital-based insurance claims database (Medical Data Vision Co. Ltd.), we conducted a retrospective cohort study for patients with these psoriasis subtypes who initiated systemic drug therapy between 2020-2023 and had a ≥ 12-month observation period. Overall, 3965 patients with plaque psoriasis, 80 with erythrodermic psoriasis, and 128 with generalized pustular psoriasis were included (median age, 62-66 years). Most patients initiated systemic therapy with a single drug. A phosphodiesterase 4 inhibitor was the most frequently prescribed index treatment for plaque psoriasis (48.8%), whereas a vitamin A derivative was most commonly prescribed for erythrodermic and generalized pustular psoriasis (42.5% and 42.2%, respectively), suggesting a distinctive Japan-specific prescription pattern. The median proportion of days covered for index treatment was nearly 100% across all subtypes. Among the index treatments, biologics generally showed longer time to discontinuation than oral medications. Elderly patients were more likely to receive a phosphodiesterase 4 inhibitor or a vitamin A derivative as index treatment than younger patients, and biologics were more commonly selected for patients with psoriatic arthritis than for those without. Early uptake of tyrosine kinase 2 inhibitor was observed in 2023. Over a median observation period of approximately 30 months, > 85% of patients received three or fewer lines of systemic drug therapy and approximately 50% remained on at least one systemic drug therapy throughout the study period. This first comprehensive Japanese claims database analysis of multiple psoriasis subtypes provides an updated real-world treatment landscape in Japan and helps address an important evidence gap arising from rapidly evolving systemic treatment options and limited contemporary real-world data.Weiterlesen

Psoriatic arthritis is a chronically progressive, inflammatory disease mediated by immunity, accompanied by severe disability, which seriously affects the patient's physical and mental health. Despite considerable advances in the treatment of psoriatic arthritis, there remains a subset of patients for whom none of the available treatments is effective. Consequently, we identified novel drug targets for psoriatic arthritis by integrating adaptive immune-related genes. We combined Mendelian randomization (MR) and summary data-based MR (SMR) analyses to explore potential drug targets of psoriatic arthritis. Cis-expressed quantitative trait loci (cis-eQTL) data as exposure factors were obtained from the eQTLGen consortium. Genome-wide association study (GWAS) summary data for psoriatic arthritis were obtained from the FinnGen database and the IEU database. Additional analyses included Bayesian colocalization, bidirectional MR, and multivariate MR (MVMR) to further strengthen the reliability of the results. Drug prediction and phenome-wide association studies (PheWAS) were employed to assess the potential of drug targets for clinical practice. Finally, protein-protein interaction (PPI) network analysis and enrichment analysis were performed to probe the functional characteristics and biological implications of potential therapeutic targets. In the discovery phase, we identified 13 adaptive immune-related genes with significant Mendelian randomization evidence for association with psoriatic arthritis, with genetically predicted higher IL6ST expression associated with increased disease risk. In the replication phase, IL6ST retained consistent direction and effect sizes across outcome, method, and exposure validation analyses. Colocalization and reverse MR provided further support for IL6ST as a genetically prioritized candidate therapeutic target for psoriatic arthritis. PheWAS and compound-gene signature enrichment analyses did not reveal strong pleiotropic associations and suggested exploratory translational context for IL6ST, whereas PPI network and enrichment analyses indicated that IL6ST and its interacting proteins are embedded in immune and inflammatory pathways implicated in psoriatic arthritis. This study identified IL6ST as a genetically supported candidate therapeutic target for psoriatic arthritis, providing certain insights into drug development for psoriatic arthritis.Weiterlesen

Anthralin ist seit vielen Jahren ein Cremewirkstoff gegen Psoriasis. Es bremst das schnelle Wachstum von Hautzellen und Plaques können sich lösen. In kranker Psoriasishaut dämpft Anthralin Entzündungen, in gesunder Haut löst es aber Reizungen über aggressive Sauerstoffteilchen aus. Forschende wollen diesen Effekt jetzt nutzen. Zusammen mit dem Wirkstoff Imiquimod kann Anthralin starke Killer T Zellen anregen, das ist spannend für neue Impfungen über die Haut und mögliche Krebstherapien. Bisher gibt es diese Daten nur aus Mausversuchen, ob das beim Menschen sicher wirkt ist offen. Originaltitel: Anthralin-From Psoriasis Drug to Power Adjuvant. Link zur Quelle

Trial number: 2023-509216-28-00 Overall trial status: Ongoing, recruitment ended Trial title: EffisayilTM ON: An open-label, long term extension study to assess the safety and efficacy of spesolimab treatment in patients with Generalized Pustular Psoriasis (GPP) Medical conditions: Generalized Pustular Psoriasis Status in each country: France:Ongoing, recruitment ended, Italy:Ongoing, recruitment ended, Germany:Ongoing, recruitment ended, Belgium:Ongoing, recruitment ended, Spain:Ongoing, recruitment ended Trial phase: Therapeutic exploratory (Phase II) Therapeutic Areas: Diseases [C] - Skin and Connective Tissue Diseases [C17] Primary end point: Occurrence of treatment emergent adverse events (TEAEs) up to week 252 of maintenance treatment Secondary end point: The reoccurrence of a GPP flare defined by GPPGA, Time to first achievement of a GPPGA score of 0 or 1 in patients who received flare rescue treatment, A GPPGA pustulation sub-score of 0 indicating no visible pustules, by visit in patients who received flare rescue treatment, Change from baseline in Psoriasis Symptom Scale (PSS) score, by visit in patients who received flare rescue treatment Age of participants: 65+ years, 0-17 years, 18-64 years Gender of participants: Female, Male Trial region: In both EEA and non-EEA Planned number of participants: 25 Sponsor: Leo Pharma A/S Sponsor type: Pharmaceutical company Trial product: Spesolimab Results posted: No Overall decision date: 12/02/2024 Countries decision date: FR: 13/02/2024, DE: 13/02/2024, BE: 19/02/2024, ES: 12/02/2024, IT: 18/03/2024 Last updated date: 28/07/2026Den kompletten Artikel zeigen

IL-17 and TNF blockade effectively treats hidradenitis suppurativa and psoriasis, yet the relative importance of the different cell types that respond to IL-17 and TNF remains unresolved. Keratinocytes are viewed as the dominant effector cells, whereas fibroblasts have recently emerged as important contributors. In mice, topical imiquimod induces IL-17- and TNF-dependent skin inflammation and models psoriasis. Here, we demonstrate that intradermal injection of IL-17 and TNF elicits inflammation with features of hidradenitis suppurativa, including a transcriptional program that is distinct from psoriasis and imiquimod-induced inflammation. Single-cell transcriptomic network analysis identified fibroblasts as the dominant communication hub in hidradenitis suppurativa and IL-17/TNF-injected mice. In contrast, fibroblasts and keratinocytes both showed strong network involvement in psoriasis and imiquimod-treated mice. Cell-type-specific deletion of IL-17RA revealed that imiquimod-induced inflammation depends equally on IL-17 signaling in fibroblasts and keratinocytes, whereas inflammation induced by intradermal IL-17/TNF requires only fibroblasts to recognize IL-17. Single-cell transcriptomic analysis of conditional knockout mice demonstrated that keratinocytes and fibroblasts activate divergent and disease-dependent transcriptional programs downstream of IL-17. These findings introduce a conceptual framework wherein IL-17 signaling is routed through distinct cellular and molecular pathways depending on disease context and establish complementary experimental systems for interrogating type 17 skin inflammation.Weiterlesen

Interleukin (IL)-17 and IL-23 inhibitors have transformed psoriasis care, delivering high clearance rates and quality-of-life gains. Nevertheless, inadequate response or adverse events can lead to treatment discontinuation or biologic switching. Dose modifications are also commonly implemented in routine practice to optimize efficacy, safety, and cost. The objective of this study is to characterize real-world outcomes of dose adjustment and switching of IL-17 and IL-23 inhibitors in Thai patients with psoriasis. We retrospectively reviewed 173 treatment courses with IL-17 inhibitors (secukinumab, ixekizumab, and brodalumab) and the IL-23 inhibitor guselkumab, documenting loading regimens, maintenance dosing, efficacy to Week 52, and switching events. At Week 12, full loading and standard maintenance dosing were associated with higher response rates in most cases. Ixekizumab was least often given with a full loading dose or standard maintenance dosing. By Weeks 24 and 52, reduced-dose regimens achieved comparable or better outcomes, suggesting careful patient selection. Thirty courses underwent biologic switching, predominantly for secondary failure. Intraclass switching among IL-17 inhibitors predominated. Switching from IL-23 to IL-17 inhibitors potentially outperformed both intraclass IL-17 switching or IL-17-to-IL-23 transitions. Erythrodermic psoriasis and higher baseline disease severity predicted switching, whereas incomplete loading doses and dose reductions did not. In conclusion, full loading and standard maintenance regimens facilitate early treatment response, while dose reduction in carefully selected patients can sustain long-term disease control without increasing the risk of switching.Weiterlesen

IntroductionThe therapeutic landscape of moderate-to-severe plaque psoriasis has been transformed by interleukin-17 (IL-17) and interleukin-23 (IL-23) inhibitors, which offer superior effectiveness compared to older biologics. However, a substantial proportion of patients experience primary or secondary treatment failure, necessitating a therapeutic switching.Areas coveredThis review integrates real-world evidence from studies identified through a PubMed search for publications on sequencing and switching between IL-17 and IL-23 inhibitors in plaque psoriasis. The most relevant studies were selected, and their clinical outcomes were evaluated to provide an overview of current evidence on switching strategies.Expert opinionKey findings indicate that interclass switching (between IL-17 and IL-23 pathways) generally outperforms intraclass switching, with IL-23 inhibitors demonstrating robust effectiveness after IL-17 failure and vice versa. Safety profiles are favorable across all switching scenarios. Future directions include biomarker-guided selection and precision medicine approaches to optimize first-line therapy choice and subsequent sequencing.Weiterlesen

IntroductionPsoriasis, a chronic immune-mediated inflammatory skin condition with systemic implications and substantial psychosocial burden, affects individuals across races and ethnicities. This study explored social drivers of health (SDOH), disease burden, and the impact of psoriasis across races and ethnicities.MethodsAn online, cross-sectional survey was conducted among adult US patients with psoriasis (September-December 2023). Participants were recruited through the National Psoriasis Foundation and AmeriSpeak, a national sample panel. Descriptive data were collected using patient-reported outcome measures and questions on disease knowledge, healthcare access and utilization, quality of life (QoL), and social impact. Analyses were stratified by races and ethnicities.ResultsAmong 285 participants (mean age 46.7 years; 50.9% male), 68.1% identified as white, 19.3% as Black/African American (BAA), and 20.4% as Hispanic/Latino (H/L). Overall, psoriasis severity was reported as moderate by 36.8% (white: 37.6%, BAA: 25.5%, Asian: 50.0%, and H/L: 27.6%) and severe by 10.2% (white: 8.2%, BAA: 10.9%, Asian: 20.0%, and H/L: 6.9%) of patients. Participants reported moderate QoL impact (Dermatology Life Quality Index [DLQI] mean 10.3), with high burden among H/L (16.6) and BAA (15.1) groups. During flares, 58.6% used prescription medications, with similar rates across races and ethnicities. Transportation barriers were reported by 21.4% overall, more commonly reported by H/L (44.8%) and BAA (34.5%) participants. Difficulty accessing medicine/healthcare was reported by 26.3% overall, particularly white (29.4%) participants. Overall, 29.1% delayed care owing to cultural/linguistic differences, most commonly by BAA and H/L groups. Of the healthcare services requiring partial out-of-pocket payment for treatment of psoriasis, medications were reported as the highest burden by an overall 47.0% of patients (H/L: ~55%, white and BAA ~45%). Overall, only 29.5% received financial assistance.ConclusionsIn this descriptive survey, patients perceived psoriasis as a considerable burden across races and ethnicities. Understanding diversities in patient-reported SDOH and healthcare access issues through culturally competent integrated care may potentially optimize psoriasis outcomes.Weiterlesen

ObjectivesWe aimed to determine whether the short-term response to biologics in biologic-naïve psoriatic arthritis (PsA) is better in patients initiating biologic treatment early in the disease course.MethodsPsA patients who started biologic therapy from the year 2000 to 2025 were included for analysis. Patients considered in the early treatment (ET) group if they started biologic therapy within 2 years of PsA diagnosis, otherwise they were considered in the delayed treatment (DT) group. The primary outcome was ≥50% reduction in the Disease Activity Index for Psoriatic Arthritis (DAPSA) score at 6-months. The secondary outcome was Psoriasis Activity and Severity Index (PASI) 75, defined as ≥75% improvement in the PASI score, at 6-months. Logistic regression was used to examine the association between early treatment and disease outcomes at 6-months. Propensity scores were used to account for differences between the groups at the baseline visit.ResultsOf the 228 included patients, 71 patients were in the ET group and 157 patients in the DT group. There were significant differences in the time from PsA diagnosis to biologic treatments over the decades. The propensity score regression adjusted analysis did not suggest a difference in response at 6 months between those treated within 2 years of diagnosis and those treated later.ConclusionShort-term response to biologic therapy in patients with PsA does not appear to differ between those treated early or later in the disease course. It remains to be determined whether early treatment prevents progression of joint damage in the longer-term.Weiterlesen

BackgroundPsoriasis is a chronic, inflammatory disease affecting up to 5% of the population. It significantly impacts patients' quality of life. In Africa, data on disease severity remain limited. The aim of this study was to evaluate the prevalence of severe psoriasis among Tunisian patients and to identify factors associated with disease severity and impairment of quality of life.MethodsA cross-sectional study was conducted using data from the Tunisian National Psoriasis registry (PsoTreg) (ClinicalTrials.gov ID: NCT05258838). A total of 1100 patients with psoriasis were included between July 12, 2022, and November 15, 2024. Disease severity and quality-of-life impairment were assessed using the Simplified Psoriasis Index (SPI). Demographic, clinical, and lifestyle data were analyzed to identify factors associated with disease severity and quality-of-life impairment.ResultsModerate-to-severe psoriasis affected 31.9% of patients, with 38.3% experiencing quality-of-life impairment. Multivariate analysis confirmed male gender (odds ratio [OR]: 2.057), psoriatic arthritis (OR: 1.693), and substance use (alcohol OR: 2.759; smoking OR: 1.609) as independent severity predictors. There were gender-specific patterns, with smoking significantly associated with severity in men and obesity with quality-of-life impairment in women.ConclusionsThis study, the first multicenter psoriasis registry in North Africa, highlighted the prevalence of moderate-to-severe psoriasis (31.9%). It emphasized a high proportion of patients with quality-of-life impairment (38.3%). Psoriasis severity was associated with smoking in men and obesity in women. These findings suggest a need for gender-tailored lifestyle interventions prioritizing mental health screening in the management of psoriasis patients.Weiterlesen

This study investigates the therapeutic efficacy of zinc sulfide nanoparticles (ZnS NPs) encapsulated within adipose-derived mesenchymal stem cell exosomes (EXO-ZnS NPs) in an imiquimod-induced rat model of psoriasis, aiming to combine nanotechnology and regenerative medicine for enhanced immune modulation and skin repair. Adipose mesenchymal stem cells (AD-MSCs) were cultured and characterized, exosomes were isolated and validated by flow cytometry and TEM. ZnS NPs were synthesized, confirmed by XRD and TEM, and encapsulated into exosomes. Release profiles, Clinical (PASI scoring), histopathological, inflammatory and proliferative markers as well as immunohistochemical analyses were evaluated across control, psoriasis, and treatment groups (EXO, ZnS NPs, and EXO-ZnS NPs). EXO-ZnS NPs exhibited a uniform nanosize with sustained ZnS NPs release (80.5% over 24 h). In vivo, EXO-ZnS NPs significantly attenuated psoriatic symptoms, and Severity Index scores, reduced inflammatory mediators (IL-23, IL-17a, TNF-α, MCP-1, NLRP3), mitigated oxidative stress, downregulated proliferative markers (Ki-67, MMP-9), and inhibited VEGF-mediated angiogenesis. collectively restored epidermal structure and improved skin architecture. EXO-ZnS NPs synergistically combine the regenerative and immunomodulatory effects of exosomes with the intrinsic anti-inflammatory and antioxidant activities of ZnS NPs, offering a novel promising, dual-action therapeutic platform for effective and sustained psoriasis management.Weiterlesen