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Neue Forschung zeigt, dass Psoriasis mehr ist als eine einfache Entzündung durch fehlgeleitete Immunzellen. Bisher dachte man, T-Zellen und bestimmte Botenstoffe wie IL-17A und IL-23 lösen die Schuppenflechte aus, indem sie Hautzellen zur Überproduktion anregen[1]. Das stimmt zwar, aber die Sache ist komplexer. Mit modernen Techniken wie Spatial Proteomics haben Forschende jetzt herausgefunden: Schuppenflechte verteilt sich auf verschiedene Hautschichten, die jeweils eigene Aufgaben und Zelltypen haben[1]. Vor allem die innere Epidermis spielt wohl eine zentrale Rolle. Dort verändern sich besonders viele Eiweiße – einige davon gehören zur Immunabwehr, andere sind wichtig für den Stoffwechsel wie die Cholesterinproduktion[1]. Auch das Zusammenspiel von Hautzellen, Bindegewebszellen und Immunzellen geschieht in Schichten und ist vielschichtiger als gedacht[4]. Dieses neue Verständnis könnte helfen, gezieltere Therapien zu entwickeln. Originaltitel: Spatial Proteomics Redefines Psoriasis as a Vertically Stratified, Immunometabolic Tissue State Link zur Quelle

Forscher haben bei Mäusen gezeigt: Fehlt das Enzym **Myeloperoxidase (MPO)**, werden Entzündungen bei **Psoriasis Arthritis** deutlich schlimmer[1]. Es kommt zu mehr Hautentzündungen, stärkeren Schwellungen an den Gelenken und sogar zu stärkerem Knochenabbau. In den betroffenen Bereichen fanden sie mehr Entzündungszellen und mehr entzündliche Botenstoffe. Normalerweise hilft MPO wohl mit, solche Entzündungen durch bestimmte Vorgänge in Abwehrzellen zu bremsen. Ohne MPO läuft das Immunsystem also besonders heiß[1]. Originaltitel: Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model. Link zur Quelle

In dieser Studie wird untersucht, wie wirksam und sicher der Wirkstoff **JNJ-77242113** bei Erwachsenen mit mittelschwerer bis schwerer Plaque-Psoriasis ist. Die Studie ist eine große, internationale Phase-3-Studie, bei der die Teilnehmer nach dem Zufallsprinzip entweder das Prüfmedikament oder ein Placebo erhalten, ohne dass sie oder die Ärzte wissen, wer was bekommt. Nach einer ersten Behandlungsphase werden einige Patienten zufällig auf ein Absetzen oder eine erneute Behandlung umgestellt, um zu prüfen, wie stabil die Wirkung ist und wie gut das Medikament bei erneutem Bedarf wirkt. **JNJ-77242113** ist eine neuartige Substanz in Tablettenform, die gezielt den sogenannten IL-23-Rezeptor blockiert. IL-23 ist ein Botenstoff im Immunsystem, der eine zentrale Rolle bei der Entstehung und Aufrechterhaltung der Entzündungsreaktionen bei Psoriasis spielt. Durch die Blockade dieses Rezeptors wird die Aktivierung bestimmter Immunzellen gehemmt, was zu einer deutlichen Verbesserung der Hautsymptome führen kann. Im Unterschied zu vielen bisherigen Therapien, die gespritzt werden müssen, handelt es sich bei JNJ-77242113 um eine Tablette, die oral eingenommen wird. Frühere Studien zeigen, dass viele Patienten unter dieser Behandlung eine nahezu vollständige oder vollständige Abheilung der Haut erreichen und die Wirkung auch über längere Zeit anhält. Die bisherigen Daten deuten außerdem auf ein günstiges Sicherheitsprofil hin. Originaltitel: A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants with Moderate to Severe Plaque Psoriasis with Randomized Withdrawal and Retreatment Erkrankung: mittelschwere bis schwere Plaque-Psoriasis Phase: III Firma: Janssen - Cilag International Art der Verabreichung: Tablette https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505120-59-00

In dieser Studie wird untersucht, wie wirksam und sicher der Wirkstoff **JNJ-77242113** bei Erwachsenen mit mittelschwerer bis schwerer Plaque-Psoriasis ist. Die Teilnehmer erhalten entweder JNJ-77242113, ein Placebo (eine Tablette ohne Wirkstoff) oder Deucravacitinib, einen bereits zugelassenen Wirkstoff gegen Psoriasis. Ziel ist es herauszufinden, ob JNJ-77242113 die Hautsymptome besser lindert als die Vergleichssubstanzen und wie gut das Medikament vertragen wird. **JNJ-77242113** ist eine neuartige Tablette, die gezielt den sogenannten IL-23-Rezeptor blockiert. IL-23 ist ein Botenstoff im Immunsystem, der bei Entzündungen und damit auch bei der Entstehung von Psoriasis eine wichtige Rolle spielt. Durch das Blockieren dieses Rezeptors soll verhindert werden, dass Entzündungsprozesse in der Haut ausgelöst werden – dadurch können Rötungen und Schuppenbildung zurückgehen. Die Studie richtet sich an Erwachsene ab 18 Jahren mit einer ausgeprägten Form von Plaque-Psoriasis (mindestens 10% Körperoberfläche betroffen). Sie verläuft doppelblind und randomisiert: Das bedeutet, weder Teilnehmende noch Ärztinnen wissen zunächst, wer welches Präparat bekommt – so lassen sich Unterschiede objektiv messen. Originaltitel: A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled and Deucravacitinib Active Comparator-controlled Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis Erkrankung: mittelschwere bis schwere Plaque-Psoriasis Phase: III Firma: Janssen - Cilag International Art der Verabreichung: Tablette (oral) https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505121-14-00

In dieser Studie wird die Wirksamkeit und Sicherheit von **JNJ-77242113** bei Menschen mit Plaque-Psoriasis untersucht, insbesondere an Körperstellen, die als „spezielle Bereiche“ gelten (zum Beispiel Kopfhaut, Gesicht oder Nägel). Die Studie ist eine Phase-3-Studie – das bedeutet, dass sie bereits in einem fortgeschrittenen Stadium der klinischen Entwicklung ist und viele Patientinnen und Patienten einbezieht. Ziel ist es herauszufinden, wie gut das Medikament im Vergleich zu einem Placebo wirkt und wie sicher es ist. **JNJ-77242113**, auch bekannt unter dem Namen Icotrokinra (oder JNJ-2113), ist eine neuartige Substanz zur Behandlung von Plaque-Psoriasis. Es handelt sich um einen sogenannten „oralen Peptid-Wirkstoff“, also ein Medikament in Tablettenform. Das Besondere daran: Es blockiert gezielt den IL-23-Rezeptor – ein Schlüsselmolekül bei der Entstehung von Psoriasis. Durch diese Blockade wird die Entzündungsreaktion im Körper reduziert, was zu einer Verbesserung der Hautsymptome führen kann. In bisherigen Studien zeigte Icotrokinra vielversprechende Ergebnisse: Ein großer Anteil der behandelten Patientinnen und Patienten erreichte nach 16 bis 24 Wochen deutlich klarere Haut oder sogar vollständige Erscheinungsfreiheit – bei gleichzeitig guter Verträglichkeit. Originaltitel: A Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of JNJ-77242113 for the Treatment of Participants with Plaque Psoriasis involving Special Areas Erkrankung: Plaque-Psoriasis Phase: III Firma: Janssen - Cilag International Art der Verabreichung: Tablette (oral) https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-505122-34-00

Neutrophile sind die häufigsten weißen Blutkörperchen im Blut und kommen als Erste zu Entzündungen oder Infektionen[1][4]. Sie können sogenannte Neutrophil Extracellular Traps (NETs) bilden[1][4]. NETs sind netzartige Strukturen aus DNA und Proteinen[1][3]. Sie fangen Keime ein und helfen, Infektionen zu bekämpfen[1][3]. Doch NETs können auch Probleme machen. Sie fördern Entzündungen und spielen eine Rolle bei Autoimmunerkrankungen wie Psoriasis sowie bei Thrombosen und Krebs[3][4]. So sind NETs wichtig, können aber auch Schaden anrichten. Originaltitel: Neutrophil Extracellular Traps (NETs) in Immunity and Diseases: Second Edition. Link zur Quelle

Background and objectivesContinuous biologic treatment is recommended for patients with psoriasis; however, treatment interruption in daily practice is inevitable. The impact of treatment interruption is difficult to study in a real-world setting. In Taiwan, biologics are reimbursed by the National Health Insurance for moderate-to-severe psoriasis for a 2-year course, followed by regulatory discontinuation. Thus, our study provides pragmatic data on the impact of the interruption of biologics treatment for non-medical reasons on therapy effectiveness.Patients and methodsThis single-center retrospective cohort study recruited patients who underwent two consecutive 2-year courses of biologics between 2012 to 2021.ResultsA total of 192 treatment courses from 61 patients were analyzed, with secukinumab and ustekinumab being the most frequently administered biologics. Among patients who continued with the same biologic across two consecutive courses, the time to achieve PASI 75 was shorter during the first course compared to the second, while overall maintenance effects remained similar. Switching to a different biologic usually produced superior results in the second course of treatment.ConclusionsAlthough the overall effectiveness after interruption and resumption of treatment with secukinumab or ustekinumab was comparable, the time to achieve PASI 75 was longer following an interruption. Continuous, uninterrupted treatment with a given biologic is therefore recommended whenever possible.Weiterlesen

No abstract supplied.Weiterlesen

Gluten-related disorders (GRDs) encompass a spectrum of clinical manifestations triggered by gluten ingestion in genetically susceptible individuals. These disorders include celiac disease (CD) and non-celiac gluten sensitivity (NCGS) and present with both intestinal and extraintestinal symptoms, including skin manifestations. Besides the well-known association between CD and dermatitis herpetiformis, considered as the cutaneous manifestation of CD, other dermatoses have been associated to GRDs. In this paper, we provide a concise overview of the clinical appearance, diagnosis and therapeutic management of GRDs, a tool which we hope will facilitate clinicians when faced with this challenging group of diseases.Weiterlesen

No abstract supplied.Weiterlesen

Tuberculosis (TB) continues to be a leading cause of death in many countries, and also remains a significant concern in Germany, particularly due to migration. The diagnosis of rare cutaneous tuberculosis is challenging as it manifests in various clinical forms that resemble more common dermatological conditions. Especially in paucibacillary forms, gold-standard diagnostic tests may yield negative results, complicating the identification of the disease. Therefore, a strong clinical suspicion based on the clinical presentation is essential for guiding further or repeated diagnostic evaluations. In this article, we present various forms of cutaneous tuberculosis, using excerpts from the image collection of the Department of Dermatology and Allergy at Biederstein, Technical University of Munich, to improve clinical recognition of cutaneous TB and raise awareness of this condition also as a potential differential diagnosis.Weiterlesen

No abstract supplied.Weiterlesen

Background and objectivesKnowledge on patient care gaps of prurigo nodularis (PN) is limited. This retrospective chart review (ADVANCE PN) investigated unmet medical needs and gaps in diagnostics, treatment, and management of patients with PN in routine care in Germany.Patients and methodsMedical records for adults newly diagnosed with PN between January 2012 and December 2022 from dermatologic clinics and office-based dermatologists were analyzed. Baseline demographics, treatment patterns, diagnostics, symptoms, patient-reported outcomes (PROs), and disease-specific scores are reported.ResultsRecords of 363 patients from 42 sites were analyzed. Median age (range) was 67 (19-95) years; most patients were female (61.7%), Caucasian (73.4%), and retired (57.3%). Overall, 209 (62.2%) patients had comorbidities (most common: hypertension [28.3%]). Clinically, most patients had nodules (81.1%) or papules (66.7%). PROs, disease-specific scores, and laboratory assessments were performed for 32 (8.8%), 12 (3.3%), and 71 (19.7%) patients, respectively. Topical corticosteroids (TCS) were the most common overall (90.9%) and first-line therapy (84.9%); for second-line therapy, 'no further treatment' was most commonly documented (58.6%).ConclusionsThe findings of ADVANCE PN indicate a high unmet need in the current state of medical care, evidenced by shortcomings in PRO assessment, PN documentation, and adherence to guidelines on PN.Weiterlesen

No abstract supplied.Weiterlesen

No abstract supplied.Weiterlesen

Secukinumab, a fully human monoclonal antibody that antagonizes interleukin-17A (IL-17A), has proven efficacious in the management of moderate to severe plaque psoriasis. Secukinumab has established itself as an effective treatment for plaque psoriasis, offering rapid and sustained symptom improvement. However, more research is warranted to assess its efficacy and safety in elderly patients, where clinical data is currently lacking. We describe an 84-year-old female presented with stable angina pectoris needed to be hospice cared. She had more than 30 years history of plaque psoriasis. The patient underwent treatment with secukinumab for two weeks. The skin lesions had been decreased rapidly and this greatly improved quality life of this patient. We report the clinical use of secukinumab in the treatment of elderly psoriasis and biologicals may be a new strategy for hospice care of patients with psoriasis.Weiterlesen

No abstract supplied.Weiterlesen

Moderate to severe psoriasis has been reported as an independent risk factor for IgA nephropathy (IgAN). IgAN is characterized by episodic microscopic hematuria, which can progress to end-stage renal disease (ESRD). Managing therapeutic interventions for psoriasis patients requiring dialysis due to ESRD presents significant challenges. We present a case of severe plaque psoriasis in a patient concurrently diagnosed with IgAN who is dependent on hemodialysis. Over the past two months, his condition has worsened without any identifiable triggers. Physical examination revealed generalized scaly plaques on the scalp, trunk, and extremities, resulting in a Psoriasis Area Severity Index (PASI) score of 19.2. Laboratory tests confirmed end-stage renal insufficiency, with no other abnormalities detected. Consequently, the patient was prescribed subcutaneous secukinumab following a standard regimen. He achieved complete resolution of symptoms after eight weeks of treatment and experienced no recurrence during a one-year follow-up. His kidney-related parameters remained stable during secukinumab therapy. To summarize, this case report discusses a patient with severe psoriasis who also has concurrent IgAN and ESRD, successfully treated with secukinumab. It reinforces the rapid efficacy and enduring safety of secukinumab in managing psoriasis in hemodialysis-dependent patients with IgAN comorbidity. Zeno Fratton et al has reported that an interleukin (IL)-17A/F inhibitor effectively treats moderate-to-severe psoriasis in patients with chronic kidney disease (CKD). However, further studies are necessary to develop evidence-based guidelines for biologic selection within this vulnerable population.Weiterlesen

BackgroundThe IL-17A inhibitors target aberrant immune responses in psoriasis but also impacts the host's defense against infections. The effects of this treatment on skin microorganisms and microbiome-encoded metabolic pathways remain unclear.ObjectivesThis was an exploratory clinical study designed to investigate whether Psoriasis is associated with skin microbiota, as well as a longitudinal cohort study aimed at revealing the effects of IL-17A inhibitor treatment on skin microbiota in Psoriasis.MethodsIn this study, we recruited 26 patients with moderate to severe psoriasis and 15 healthy controls. We collected skin microbiome samples from both greasy and dry skin regions. All samples were analyzed using 16S rDNA gene sequencing to determine the microbial profiles.ResultsCompared with healthy controls, the composition and function of skin microbiome in psoriasis patients are heterogeneous. Treatment with IL-17A inhibitors significantly increases the alpha diversity of the skin microbiota in psoriasis patients, indicating potential restoration of microbial community richness and evenness. However, this treatment does not entirely alter the taxonomic composition of the skin microbiota; rather, it shifts the relative abundance of specific microbial species, indicating that certain core microbial features remain relatively stable. Moreover, IL-17A inhibitors help adjust the functional profile of the skin microbiome in psoriasis patients, bringing it closer to that of healthy individuals.ConclusionsPsoriasis patients exhibit significant heterogeneity in both the composition and functionality of their skin microbiota. Although IL-17A inhibitor treatment fails to fundamentally alter its taxonomic composition, this therapy effectively enhances microbial community stability by increasing alpha diversity and modulating the relative abundance of various taxa. Additionally, it adjusts the functional profile of the skin microbiota towards a healthier state, thereby contributing to the restoration of microecological balance.Weiterlesen

Topical drugs containing corticosteroids are recommended first-line treatment for patients with mild-moderate psoriasis. However, the optimal recommended dosage of topical drugs has not been well established. To investigate the effect of topical drug application quantity and treatment duration on psoriasis treatment outcome. We conducted a post-hoc analysis of two randomized controlled trials investigating 214 patients with psoriasis using topical drugs containing corticosteroids and/or calcipotriol for up to 48 weeks. We measured the amount of topical drugs used during the study period and calculated the mean amount of applied drugs per 1% affected body surface area (BSA) divided by number of days in the study period. Improvement in severity of psoriasis was measured by Lattice-System Physician's Global Assessment (LS-PGA) (where affected BSA was divided into seven categories) from baseline to last study visit. Descriptive results were reported as counts with proportions, and as means with normality-based confidence intervals (CI). Associations were analyzed using linear regressions. Most study participants had a duration of psoriasis greater than 20 years, moderate psoriasis, and no history of using systemic psoriasis treatment. They had applied a mean of 1.0 g per 1% BSA per day (95% CI 0.9; 1.2). Daily use of topical drugs for four-weeks reduced severity of psoriasis. However, extended daily use for up to 48 weeks provided further reduction in disease severity (coefficient --0.30 (95% CI -0.51, -0.09)) and -0.73 (95% CI -1.09; -0.38) (P= 0.028). Greater amount of applied topical drugs reduced severity of psoriasis in a linear manner. Every increase of 1 g of topical drugs applied per 1% BSA per day reduced LS-PGA by 0.43 (95% CI 0.24; 0.61). Finally, patients who had never used systemic drugs experienced a greater reduction in psoriasis when applying the same mean amount of topical drugs (coefficient -0.7 (95% CI -1.1, -0.4) compared to those who had a history of taking systemic treatment (-0.3 (95% CI -0.5; -0.1), P=0.026). A mean application amount of at least 1.0 g of topical drugs per 1% BSA per day seems safe and effective and can be used daily until clearance.Weiterlesen

We developed and validated a novel analytical methodology for the precise quantification of deucravacitinib, an oral TYK2 inhibitor for treating moderate-to-severe plaque psoriasis in adults. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in this method for sensitive detection of the compound in rat plasma. Analytical separation was performed utilizing an ACE C18 column (4.6 × 100 mm, 5-μm particle size) with a carefully optimized mobile phase composition of methanol and 2-mM ammonium formate (90:10, v/v), maintained at a consistent flow rate of 0.9 mL/min. Detection was executed in positive ionization mode, targeting multiple reaction monitoring (MRM) transitions of m/z 426.8 → 358.4 for the analyte and m/z 394.1 → 363.2 for the internal standard. The validation of the analytical method encompassed an assessment of selectivity, linearity, accuracy, precision, recovery, and stability. This method demonstrated stability, specificity, and no matrix effect at three concentration levels (1.606, 267.600, 507.780 ng/mL). The method's lower limit of quantification (LLOQ) is 0.556 ng/mL. The calibration curve demonstrates linearity from the LLOQ up to 668.132 ng/mL, exhibiting a high correlation coefficient (r2 = 0.9976). The intraday and interday precisions were less than 6.62% and 5.95%, respectively, with accuracies ranging from 90.68% to 103.80%. The recovery of deucravacitinib ranged from 95.34% to 103.80% and remained stable under different conditions. After successful validation, the method was used for pharmacokinetic profiling of deucravacitinib in rats following oral administration.Weiterlesen

No abstract supplied.Weiterlesen

Down syndrome (DS), also known as trisomy 21, is a genetic condition linked to a higher prevalence of skin disorders, including psoriasis, which affects up to 8% of individuals. DS patients with psoriasis present unique management considerations, including a theoretical increased risk of infectious complications with immunosuppressive therapies. This report includes two cases and a systematic review summarizing available evidence on psoriasis characteristics and treatment outcomes in individuals with DS. We report two DS patients with psoriasis demonstrating variable therapeutic responses: one controlled with acitretin and another requiring secukinumab after multiple treatment failures. To contextualize these findings, we conducted a systematic review following PRISMA guidelines, identifying 10 studies comprising 37 DS patients with psoriasis. Methotrexate was the most frequently failed therapy. Biologics targeting IL-17 and IL-23 pathways achieved the highest rates of complete resolution. These findings reflect Th1/Th17-driven inflammation in DS and highlight the need for individualized, pathway-specific management strategies.Weiterlesen

IntroductionPsoriasis is a chronic immune-mediated skin condition that has a substantial impact on patients' quality of life. The Saudi Arabia Psoriasis Registry (PSORSA) was established to address long-term real-world data (RWD) on systemic and biologic therapies in the region. This observational cohort study provides a comprehensive analysis of baseline disease characteristics, comorbidities, and treatment efficacy among patients enrolled in PSORSA, with an emphasis on risankizumab.MethodsData were sourced from a governmental online database covering multiple healthcare centers. Patients eligible for biologics were followed at baseline and at weeks 16, 28, 40, and 52 to evaluate disease severity, quality of life, and adherence. Statistical analyses were conducted using Jamovi and R. Descriptive statistics were performed for categorical and continuous variables. p-Values < 0.05 were considered significant.ResultsThe study cohort included 313 patients. Plaque psoriasis was the most prevalent clinical type (93.9%). An analysis of treatment history revealed that 39.6% of patients had prior therapy exposure, and all patients received risankizumab as a biologic therapy. At baseline, the mean Psoriasis Area and Severity Index (PASI) score was 25.49. By week 52, it had decreased to 0.358, indicating complete clearance. PASI scores showed a steady and substantial reduction over time, with an 88% reduction at week 16, 96% at week 28, 97.5% at week 40, and 98.5% by week 52, demonstrating a strong and sustained treatment effect (p < 0.001). Additionally, risankizumab exhibited a favorable drug survival profile, with many patients maintaining treatment beyond 122 weeks.ConclusionThis study represents the first real-world assessment of risankizumab for moderate-to-severe psoriasis in Saudi Arabia. The findings demonstrate that risankizumab is an effective and well-tolerated treatment for moderate-to-severe psoriasis in this Saudi Arabian cohort. However, future studies should explore long-term safety outcomes and the comparative effectiveness of risankizumab and emerging biologics in diverse patient populations.Weiterlesen

Wer seine Schuppenflechte (Plaque-Psoriasis) mit Biologika behandelt, sollte die Therapie am besten ohne Pause fortführen. Im Alltag lassen sich Unterbrechungen aber nicht immer vermeiden[2]. Nach einer Pause kann es länger dauern, bis die Haut wieder so gut wird wie vorher. Die Wirkung von Secukinumab oder Ustekinumab bleibt nach Wiedereinstieg zwar ähnlich, aber der Zustand bessert sich langsamer[2]. Wer nach einer Therapiepause auf ein anderes Biologikum wechselt, erzielt oft sogar bessere Ergebnisse als zuvor[2]. Trotzdem empfehlen Fachleute, möglichst keine unbeabsichtigten Unterbrechungen zu machen, weil eine durchgehende Behandlung schneller und verlässlicher wirkt[2]. Wechsel zwischen verschiedenen Biologika sind keine Seltenheit: Hauptgrund dafür ist meist, dass das Mittel nicht mehr genug wirkt[4]. Adalimumab und Ustekinumab gehören oft zu den am meisten genutzten Präparaten[4]. Originaltitel: Optimizing biologics for chronic plaque psoriasis: insights on non‐medical interruptions of IL‐17, IL‐12/23, and IL‐23 inhibitors Link zur Quelle