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Menschen mit Diabetes, die sogenannte **GLP-1-Rezeptor-Agonisten** (zum Beispiel Ozempic oder Wegovy) einnehmen, bekommen seltener **Psoriasis** oder **Hidradenitis suppurativa**. Das zeigen neue Untersuchungen[1][2][3][4]. Die Medikamente wirken eigentlich gegen Diabetes und helfen beim Abnehmen. Sie haben aber auch einen positiven **Einfluss auf Entzündungen** im Körper und damit auf manche Hautkrankheiten. Forscher haben herausgefunden, dass Patienten mit diesen Medikamenten nicht nur besser ihren Blutzucker kontrollieren, sondern auch weniger Hautprobleme bekommen. Die Wirkung ist nicht nur auf das Abnehmen zurückzuführen. Die Medikamente bremsen direkt Entzündungen, die bei Psoriasis und Hidradenitis suppurativa eine wichtige Rolle spielen. Manche Menschen berichten sogar schon vor starkem Gewichtsverlust von einer Besserung ihrer Haut[2][3]. Wichtig zu wissen: Nicht jeder spürt eine Verbesserung, aber gerade wenn Übergewicht und Hautkrankheit zusammen auftreten, lohnt sich ein Gespräch mit dem Arzt. Originaltitel: Decreased incidence of hidradenitis suppurativa and psoriasis in diabetic patients treated with GLP-1 receptor agonists: A retrospective cohort study Link zur Quelle

TNF-Blocker (TNFi) wie Adalimumab oder Etanercept werden oft bei Psoriasis-Arthritis eingesetzt. Viele hatten Sorge, dass sie das Gewicht steigen lassen. Eine neue Studie zeigt aber: Menschen mit Psoriasis-Arthritis nehmen unter TNFi nicht mehr zu, als es sowieso mit dem Alter üblich ist[1][5]. Im Schnitt haben die Patienten zwar in den Jahren nach Beginn der Therapie ein paar Kilo zugenommen, das lag aber im normalen Bereich und war nicht auf das Medikament zurückzuführen. Entscheidend: Wer TNFi nimmt, muss eine Gewichtszunahme nicht befürchten – und falls doch, sollte zuerst mit dem Arzt gesprochen werden. Bei anderen Biologika oder Wirkstoffen kann die Auswirkung aufs Gewicht übrigens anders sein[3]. Originaltitel: Changes in weight associated with tumor necrosis factor inhibition in psoriatic arthritis: results from a retrospective cohort study - Clinical Rheumatology Link zur Quelle

Manche Menschen sprechen besonders gut auf Psoriasis-Medikamente an, sie heißen „Super-Responder“[1][3]. Super-Responder haben nach 12 Wochen fast immer komplett gesunde Haut, wenn sie das richtige Biologikum bekommen. Forscher haben jetzt untersucht, wie oft das passiert und welches Medikament am besten wirkt. In dieser neuen Studie bekamen 116 Erwachsene mit mittlerer bis schwerer Psoriasis ihr erstes Biologikum. Nach 12 Wochen hatten 26 von ihnen (etwa jeder Fünfte) komplett erscheinungsfreie Haut. Das beste Ergebnis zeigte **Bimekizumab**: Von 17 Patienten waren 11 Super-Responder – also fast zwei Drittel. Mit anderen Biologika waren es deutlich weniger[2]. Ob jemand Super-Responder wird, lag vor allem am ausgewählten Medikament. Alter, Geschlecht oder wie lange jemand schon Psoriasis hat, spielten keine Rolle. Die Forscher sagen: Das Wirkprinzip des Medikaments ist entscheidend dafür, wie schnell und wie gut die Haut heilt[2]. Für Menschen mit Psoriasis könnte das bedeuten: Die Wahl des Medikaments macht einen großen Unterschied, besonders am Anfang der Behandlung[2]. Originaltitel: Super Responders in Plaque Psoriasis: A Real-World, Multi-Agent Analysis Showing Bimekizumab Associated with the Highest Odds of PASI = 0 at Week 12 Link zur Quelle

Semaglutid kann Menschen mit Psoriasis und Übergewicht helfen, die Krankheit besser zu kontrollieren und gleichzeitig abzunehmen[2][6]. In Studien verbesserte sich das Hautbild deutlich, die entzündeten Stellen wurden kleiner und der Allgemeinzustand stieg spürbar[2]. Zusätzlich verloren die Patienten Gewicht, was die Symptome der Psoriasis weiter abschwächen kann[1][2]. Semaglutid wirkt nicht nur gegen Diabetes, sondern hemmt auch Entzündungen im Körper[2]. Experten vermuten, dass dadurch weniger Entzündungsbotenstoffe in der Haut entstehen. Die bisherigen Ergebnisse sind positiv, aber es gibt noch wenige große Studien. Semaglutid wird aktuell als Zusatz zu Ernährung und Bewegung bei Übergewicht eingesetzt und könnte eine neue Behandlungsmöglichkeit für einige Menschen mit Psoriasis sein[3][4][6]. Originaltitel: Dermatologic and Metabolic Benefits of Semaglutide in Psoriasis with Obesity: A Six-Month Prospective Cohort Study | Clinical and Experimental Dermatology | Oxford Academic Link zur Quelle

Roflumilast Creme 0,3 % hilft bei chronischer Plaque-Psoriasis deutlich besser als ein Placebo. In Studien mit Menschen ab 2 Jahren, die 2–20 % ihrer Haut betroffen hatten, trugen die Teilnehmenden die Creme einmal täglich für 8 Wochen auf. Nach dieser Zeit erreichten 40 % der Roflumilast-Gruppe ein deutliches Nachlassen der Psoriasis (PASI-75), während das bei der Vergleichsgruppe nur 6,5 % schafften. Mit dem genaueren PASI-HD-Wert waren es sogar rund 60 % gegenüber 18 % der Placebogruppe. Besonders auffällig: Mit PASI-HD lassen sich die Verbesserungen besser erkennen, wenn größere Hautflächen betroffen sind. Insgesamt führte die Behandlung mit Roflumilast zu deutlich weniger und weniger schweren Psoriasis-Stellen als beim Placebo[1]. Originaltitel: Roflumilast Cream 0.3% in Patients with Chronic Plaque Psoriasis: Pooled PASI and PASI-HD Results from the DERMIS Phase III Trials - Dermatology and Therapy Link zur Quelle

Forschende haben ein Modell entwickelt, das vorhersagen kann, wie gut Menschen mit Psoriasis-Arthritis auf bestimmte Medikamente ansprechen. Dafür wurden Daten von 80 Betroffenen ausgewertet, die entweder erstmals oder nach Versagen einer Vorbehandlung Methotrexat, Tofacitinib oder Etanercept bekommen haben. Sie schauten, wer nach 16 Wochen die Krankheitsaktivität stark senken konnte. Besonders bei einem hohen Wert im Gesundheitsfragebogen, vielen schmerzhaften Gelenken, vielen schmerzenden Sehnenansätzen, schlechter Einschätzung durch die Ärztin sowie früheren Therapien mit TNF-Blockern war die Chance auf Besserung geringer. Für die meisten, die noch nie DMARDs bekommen hatten, war die Chance mit Methotrexat besser als mit Tofacitinib. Wer schon andere Mittel ohne Erfolg hatte, sprach auf Etanercept meist besser an als auf Tofacitinib. Das Modell soll bald weiter verbessert werden[1][2]. Originaltitel: The development of a clinical prediction model for response to methotrexate, tofacitinib, and etanercept in patients with Psoriatic Arthritis - Arthritis Research & Therapy Link zur Quelle

Menschen mit Psoriasis haben öfter auch Fibromyalgie als gesunde Menschen[4]. Fibromyalgie tritt vor allem bei Frauen mit Psoriasis auf und besonders häufig, wenn zusätzlich eine Psoriasis-Arthritis vorliegt[4]. Wer beide Krankheiten hat, braucht öfter eine Therapie mit Biologika und muss Behandlungskonzepte häufiger wechseln[4]. Im Vergleich zu Psoriasis-Patienten ohne Fibromyalgie ist die Behandlung komplizierter. Viele spüren stärkere Schmerzen und bekommen öfter und schneller neue Medikamente, weil die erste Therapie weniger lange wirkt (im Schnitt 6 statt 10 Jahre)[4]. Bei Psoriasis-Arthritis und Fibromyalgie sind Müdigkeit, Schlafstörungen und Konzentrationsprobleme besonders häufig[1]. Die Beschwerden betreffen den Alltag und verschlechtern die Lebensqualität. Therapien müssen deshalb individuell angepasst werden, damit Betroffene bestmöglich unterstützt werden[4]. Originaltitel: The Association Between Psoriasis, Psoriatic Arthritis, and Fibromyalgia Syndrome: Effects on Treatment—A Population-Based Study Link zur Quelle

Eine große Studie aus den USA zeigt, dass Frauen mit Psoriasis oft niedrigere Spiegel von weiblichen Geschlechtshormonen im Blut haben als gesunde Frauen[5][7]. Besonders betroffen sind die Hormone **Östrogen** und **Progesteron**. Das kann erklären, warum viele Frauen merken, dass ihre Psoriasis vor den Tagen oder nach den Wechseljahren schlimmer wird[1][3]. Bei einer Schwangerschaft, wenn Östrogen besonders hoch ist, berichten dagegen viele, dass sich die Haut verbessert[3][9]. Die Forscher betonen: Die Schwankungen der Hormonspiegel beeinflussen vermutlich, wie aktiv die Krankheit ist[3][6]. Je weniger weibliche Hormone im Blut sind, desto stärker scheint die Schuppenflechte zu sein[5]. Originaltitel: Negative association of psoriasis with female sex hormone levels: a case-control study using TriNetX Link zur Quelle

Eine neue Studie zeigt: Viele Menschen mit Psoriasis fühlen sich immer noch nicht gut genug behandelt, obwohl es schon viele Medikamente gibt[1][2][3][5]. Mehr als die Hälfte der Befragten sagt, die Krankheit macht ihren Alltag schwer[3]. Egal ob Erwachsene oder Jugendliche – viele wünschen sich andere Therapien. Rund 50 Prozent der Patientinnen und Patienten und fast genauso viele Hautärzte hätten am liebsten eine Tablettenbehandlung, die stark und sicher wirkt[1][2][3][5]. Vor allem: Wer gerade Spritzen bekommt, würde zu 90 Prozent auf Tabletten umsteigen, wenn sie genauso helfen[1][5]. Bequemlichkeit und Sicherheit spielen dabei eine wichtige Rolle[3]. Die Studie macht deutlich: Es braucht noch mehr passende und einfache Therapien, damit das Leben mit Schuppenflechte leichter wird[2][3]. Originaltitel: New study reveals substantial unmet need in psoriasis, shows strong patient and provider preference for highly effective oral treatments with favorable safety profile Link zur Quelle

Digitale Gesundheits-Apps können Menschen mit Psoriasis oder Psoriasis-Arthritis beim Umgang mit ihrer Erkrankung unterstützen[1]. Es gibt Apps, die Hautsymptome dokumentieren, wie Sorea oder Psoriasis Monitor, sowie Apps für Gelenkbeschwerden, zum Beispiel Mida Rheuma App oder Rheuma-Auszeit[1]. Lern-Apps wie PSO Kiosk und Therapie-Begleiter wie MyTherapy runden das Angebot ab[1][5]. Die Apps helfen, die Krankheit besser zu verstehen, am Ball zu bleiben und sich mental wohler zu fühlen. Keine App ist bisher als DiGA zugelassen, aber sie können im Alltag trotzdem nützlich sein[1]. Originaltitel: [Medical health apps for psoriasis and psoriatic arthritis]. Link zur Quelle

IntroductionPsoriasis (PsO) in the genital and scalp areas is associated with increased patient burden and impact on quality of life. Effective treatments for PsO in these high-impact areas are essential, though patients are frequently excluded from both biologic clinical trials and treatment because of their often low overall affected body surface area (BSA) despite the disproportionate impact of PsO on their quality of life. Recent guidance also considers these patients as candidates for advanced therapies. Here, we compare the efficacy and safety of risankizumab, an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis, versus placebo in the treatment of PsO in the genital or scalp region.MethodsUnlIMMited (NCT05969223) is an ongoing phase 4, multicenter, randomized, double-blind, placebo-controlled study for adult patients with moderate-to-severe genital or scalp PsO in patients with < 10% BSA or ≥ 10% BSA involvement. Two parallel studies were conducted with study-G assessing genital PsO and study-S assessing scalp PsO. Patients were randomized 1:1 within each study to receive either 150 mg risankizumab or placebo at weeks 0 and 4. The primary endpoints for the studies were the achievement of static Physician's Global Assessment - Genital (sPGA-G) 0/1 for study-G and scalp Investigator Global Assessment (IGA) 0/1 for study-S, both assessed at week 16. Secondary endpoints are also reported at week 16 in each study assessing skin clearance, symptom resolution, and impact on quality of life. Safety was reported through the first 16 weeks.ResultsAt week 16, in both studies, a significantly higher proportion of patients receiving risankizumab achieved the primary endpoints compared with placebo. In study-G, 69.1% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved sPGA-G 0/1 (P < 0.0001). In study-S, 60.8% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved scalp IGA 0/1 (P < 0.0001). No new safety signals were identified.ConclusionThese results demonstrate that risankizumab is effective in the treatment of genital and scalp psoriasis at week 16, with no new safety signals identified.Trial registration numberClinicalTrials.gov identifier NCT05969223.Weiterlesen

IntroductionMental health status potentially influences treatment responses. The effect of probable anxiety and/or depressive disorder (pADD) on tofacitinib efficacy, patient-reported outcomes (PROs), and safety in psoriatic arthritis (PsA) was assessed.MethodsThis was a post hoc analysis of two phase 3 trials in patients with PsA receiving tofacitinib, adalimumab, or placebo, and an open-label extension study. Outcomes were stratified by presence/absence of baseline pADD (Short Form-36 Health Survey [SF-36] Mental Component Summary score ≤ 38/ > 38). American College of Rheumatology ≥ 20%, ≥ 50%, and ≥ 70% (ACR20/50/70) responses, remission and/or low disease activity based on Psoriatic Arthritis Disease Activity Score and Disease Activity Index for Psoriatic Arthritis score, minimal disease activity, and PROs (pain/Health Assessment Questionnaire-Disability Index/fatigue) were assessed through month 36. Safety was assessed through month 12.ResultsOverall, 323/706 (45.8%) patients had baseline pADD; of these, a higher proportion were female versus male (61.9% vs. 38.1%). Numerically higher proportions achieved efficacy/PRO responses with tofacitinib versus placebo, regardless of baseline pADD (month 3). Responses with tofacitinib were generally similar in patients with versus without baseline pADD (e.g., month 3 ACR20 responses: 54.0% vs. 58.5%); some differences were observed at later time points (e.g., month 9 minimal disease activity: 25.0% vs. 43.8%; p < 0.05). Baseline pADD did not appear to affect the incidence of treatment-emergent adverse events.ConclusionsBaseline pADD was frequent in patients with PsA initiating tofacitinib and was higher in female patients. Tofacitinib-treated patients had generally similar efficacy/safety outcomes, regardless of baseline pADD. Some differences in efficacy outcomes were noted in the longer term (9-12 months). Limitations of this study include small numbers in some analyses and use of SF-36 as pADD proxy.Trial registrationClinicalTrials.gov: NCT01877668; NCT01882439; NCT01976364.Weiterlesen

ObjectiveTo investigate the association between peripheral disease activity and pre-eclampsia, gestational hypertension, preterm birth and fetal growth in women with psoriatic arthritis (PsA).MethodsData from a Norwegian nationwide register (RevNatus) were linked with data from the Medical Birth Registry of Norway (MBRN). Cases were singleton births in women with PsA with available disease activity assessment (n=109) included in RevNatus 2010 to 2019. Singleton births registered in MBRN during the same decade served as population controls (n=575 798). Disease activity was assessed by Disease Activity Score based on 28 joints using C reactive protein (DAS28-CRP) in 2nd and 3rd trimester. Active PsA was defined as DAS28-CRP≥2.6 (n=34) and inactive PsA as DAS28-CRP<2.6 (n=75).ResultsPre-eclampsia was most frequent in women with active PsA (3/34, 8.8%), with a risk difference of 6.1% (95% CI 0.3 to 20.3, p=0.036) compared with population controls (2.6%). Gestational hypertension occurred in 2/34 (5.9%) of women with active PsA, with a risk difference of 4.2% (95% CI 0.0 to 17.4, p=0.065) compared with population controls (1.7%). Pre-eclampsia and gestational hypertension occurred in similar proportions in women with inactive PsA (1.3%, p=0.59 and 2.7%, p=0.24, respectively) and population controls. The occurrence of preterm birth and abnormal fetal growth was comparable in cases and population controls.ConclusionHypertensive disorders of pregnancy occurred more often in women with active, but not inactive PsA. We found no increased risk for preterm birth or abnormal fetal growth in women with PsA.Weiterlesen

Online health information (OHI) in dermatology often exceeds the recommended sixth-grade reading level, hindering patient comprehension. This study aimed to assess the utility of three artificial intelligence large language models (LLMs) - ChatGPT-3.5, ChatGPT-4, and Google Gemini - in enhancing the readability of OHI on generalized pustular psoriasis (GPP) while preserving the reliability and quality of the source material. Texts from the top 20 search results for GPP were reworded by LLMs to a sixth-grade level and evaluated using the enhanced DISCERN instrument and readability indices. Pairwise comparisons of means for each reading scale and DISCERN scores with Tukey's test were also performed. All LLMs significantly reduced readability (p<0.01) but scored lower on the DISCERN instrument compared to the original text (p<0.01). While LLMs improved readability, they did not preserve the original content's reliability and quality. These findings suggest hesitancy in using LLMs for dermatological patient education.Weiterlesen

IntroductionCardiovascular disease is a leading co-morbidity in psoriasis patients. The cutaneous benefits of biologic therapies for severe plaque psoriasis are well-established, but the impact of biologics on major adverse cardiovascular events (MACE) in psoriatic patients requires further elucidation. This study aimed to investigate the impact of biologic therapies on the risk of MACE in patients with chronic plaque psoriasis.MethodsWe conducted a systematic review and meta-analysis on 10 May 2022, using Medline, PubMed, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR) and EMBASE databases for relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology was applied, and all studies were critically appraised. All studies selected for inclusion were randomised control trials (RCTs) that contained data on MACE and compared licensed biologic therapies with placebo or other biologics in adults with moderate-severe plaque psoriasis.ResultsThe search of the databases revealed 36 papers (reporting on 43 RCTs) which met the inclusion criteria. No statistically significant difference in the risk for MACE between biologic therapies and placebo was found [Peto odds ratio (POR) 1.26, 95% confidence interval (CI) 0.53-3.01, P = 0.59]. A comparison of specific types of biologics also revealed no significant effect in adult patients with moderate-to-severe plaque psoriasis: tumour necrosis factor (TNF)-alpha inhibitors (adalimumab, infliximab, etanercept) (POR 1.13, 95% CI 0.29-4.32 P = 0.86), interleukin (IL)-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) (POR 0.60, 95% CI 0.16-2.25, P = 0.45); IL 12/23 inhibitors (usetekinumab) (POR 3.80, 95% CI 0.37-39.44, P = 0.26) and IL-23 (guselkumab, risankizumab, tildrakizumab) (POR 1.75, 95% CI 0.25-12.43 P = 0.58).ConclusionsAnti-psoriatic biologics were not associated with an increased risk of MACE in psoriasis patients. Given that most included RCTs were of relatively short duration, longer-term studies and post-marketing surveillance are needed to clarify the cardiovascular safety profile of biologic therapies. Further large-scale studies with extended follow-up are warranted.Study registrationThis study was prospectively registered on PROSPERO (identification number CRD42022325792).Weiterlesen

Mitochondrial structural and functional changes accompany psoriasis, yet the mitochondrial response to psoriatic inflammation in keratinocytes and fibroblasts remains unexplored. In this study, we investigated the effect of psoriasis-like inflammation (PLI) induced by a cytokine cocktail (interleukin (IL)-17A, IL-22 and tumour necrosis factor (TNF)-α) on mitochondrial network morphology and function in cultured keratinocytes (HaCaT) and fibroblasts (BJ-5ta). In both cell types, PLI triggered the expression of psoriasis-related Elafin and high amounts of cytokines (IL-1, IL-6), interferons (IFN-α, IFN-β, IFN-γ), and chemokines (C-C motif chemokine 5 (CCL5) and IL-8), accompanied by increased mitochondrial membrane potential, reactive oxygen species (ROS) production, respiration suppression, network fragmentation, swelling and cristae disassembly. Stimulated emission depletion (STED) nanoscopy revealed the disappearance of mitochondrial cristae in response to PLI, with the process starting more quickly and being more pronounced in keratinocytes than in fibroblasts. These findings highlight cell-specific mitochondrial responses to psoriatic inflammation, guiding future investigations towards new pharmacological targets for managing psoriasis.Weiterlesen

BackgroundPsoriasis is a chronic inflammatory skin disease often associated with obesity and metabolic dysfunction, which may worsen disease severity. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have shown metabolic and anti-inflammatory effects, but their impact on psoriasis in non-diabetic patients with obesity remains unclear.ObjectiveTo evaluate the effects of a six-month semaglutide treatment on psoriasis severity and clinical, metabolic, inflammatory, and psychosocial parameters in patients with psoriasis and obesity.MethodsIn this prospective cohort study, 43 patients received weekly semaglutide along with lifestyle counseling. Psoriasis severity (PASI), quality of life (DLQI), depressive symptoms (BDI), nutritional ultrasound, and biochemical markers were assessed baseline and after six months. Correlations between PASI improvement (ΔPASI) and baseline variables and their changes were analyzed, adjusting for age and weight loss.ResultsAfter six months, participants showed significant reductions in PASI (-48%), BMI, preperitoneal and superficial fat, along with improvements in DLQI, BDI, and metabolic markers. Baseline disease severity, depressive symptoms, insulin resistance, and preperitoneal fat were negatively associated with PASI improvement. These associations remained significant after adjustment (e.g., HOMA-IR, r = -0.82; preperitoneal fat, r = -0.66). ΔPASI was most strongly correlated with reductions in superficial fat (r = 0.89), DLQI (r = 0.55), and BDI (r = 0.51). Changes in BMI and glycemic markers were not significantly associated after adjustment.ConclusionsIn patients with psoriasis and obesity, semaglutide improves both skin disease and systemic health. The clinical benefit appears associated with specific fat loss and psychosocial improvement, beyond overall weight reduction.Weiterlesen

PurposeTo seek recommendations from a panel of experts in psoriatic arthritis (PsA) on the current management challenges, local practices, and role of interleukin (IL)-17 inhibitors in the United Arab Emirates (UAE) using evidence from phase III trials as background.MethodsNine rheumatologists who treat PsA in the UAE completed a structured survey and attended a meeting to discuss topics/issues identified in the survey. A literature search was performed to identify phase III randomized trials of IL-17 inhibitors available in the UAE for PsA.ResultsThere was general agreement among the panel on the most common PsA domains presenting in patients (most commonly psoriasis [75-95% of patients], peripheral arthritis [50-90%], and enthesitis [40-90%]). In general, IL-17 inhibitors were among the preferred treatment options for managing PsA, particularly for patients with axial-, enthesitis-, or psoriasis-related symptoms. Current unmet needs and challenges included a lack of disease awareness among the general population and other healthcare professionals; the lack of a single medication to cover all domains/comorbidities; and lack of universal insurance coverage. The panel had experienced success with the IL-17 inhibitors ixekizumab and secukinumab, with many citing no preference for either agent. The literature search identified publications relating to 10 key phase III clinical trials of IL-17 inhibitors.ConclusionThe panel advocates for the use of the domain-based Group for Research and Assessment of Psoriasis and Psoriatic Arthritis treatment recommendations and generally considers IL-17 inhibitors (ixekizumab or secukinumab) as the preferred treatment options for managing PsA.Weiterlesen

Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (TH17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a TH2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by TH2/TH17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined TH2/TH17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.Weiterlesen

ObjectiveThe concept of severity in psoriatic arthritis (PsA) remains inconsistently defined, often conflated with disease activity. This scoping review aimed to explore how severity has been defined in the PsA literature and to identify criteria used to characterize severe disease.MethodsA scoping review was conducted in April 2025 following PRISMA-ScR guidelines. PubMed was searched for English-language articles from the last 25 years, alongside abstracts from major rheumatology conferences. Eligible studies had to explicitly define or discuss PsA severity. Articles focusing solely on activity, isolated disease manifestations, or other conditions were excluded. Data were extracted on the type of article, definitions of severity, and criteria used.ResultsOf 4,014 records screened, 32 studies met inclusion criteria. Definitions of severity varied widely and were categorized into imaging (e.g., erosions), clinical (e.g., dactylitis, joint counts), and functional (e.g., HAQ-DI scores) criteria. The most commonly used indicators were structural damage, polyarticular involvement, dactylitis, arthritis mutilans, and validated composite indices such as CPDAI. Only a few studies incorporated functional impairment or patient-reported outcomes. While some guidelines, including GRAPPA and ACR/NPF, proposed multidomain frameworks, a standardized definition remains lacking.ConclusionThe concept of PsA severity has evolved beyond mere disease activity to encompass long-term outcomes, radiographic damage and overall disease burden. However, considerable heterogeneity persists across studies, reflecting the complexity of PsA. A standardized, multidimensional definition of severity, distinct from disease activity, would enhance patient stratification, guide treatment decisions, and support clinical research.Weiterlesen

ObjectivesSeveral studies have reported weight gain with tumor necrosis factor inhibitors (TNFi) in psoriatic disease. However, such analyses have not accounted for the natural propensity for weight gain over time. We aimed to investigate whether therapy with TNFi in psoriatic arthritis (PsA) patients is associated with a change in the rate of weight gain post-treatment initiation.MethodsWe included patients with at least two weight measurements prior to, and after commencing TNFi and used change point analysis to assess the differences in the rate of weight gain based on the mean slope before and after TNFi initiation, adjusting for clinically relevant variables.ResultsOf 234 patients eligible for inclusion, 62.8% were males. At the first clinic visit, the mean (standard deviation) age was 41.8 (12.2) years, while the mean disease duration was 5.1 (6.8) years. The mean weight immediately prior to TNFi use was 83.8 (17.2) kg, while that at the last available visit on TNFi was 86.4 (18.6) kg (p = 0.39), over an average period of 7.9 (5.8) years. The mean values of the pre- and post-TNFi slopes were 0.52 (95% confidence interval [CI] 0.18-0.87) and 0.28 (95% CI - 0.05-0.61), respectively (p = 0.09); thus, there was a trend towards lower rate of weight gain followed the initiation of TNFi therapy.ConclusionsTNFi treatment is not associated with an increase in weight above the expected gain in PsA. Prior trajectory of weight gain with age must be considered while studying the impact of treatment on weight.Key points• TNFi are commonly used in the management of psoriatic disease and may influence body weight. • TNFi treatment is not associated with a significant increase in body weight when accounting for the trend of weight gain with time. • The trends in weight change may differ between etanercept and monoclonal antibody TNFi agents.Weiterlesen

Background: Psoriasis is a systemic inflammatory disease associated with metabolic dysregulation. Understanding these metabolic changes may reveal biomarkers to elucidate disease mechanisms and predict comorbidities. While previous studies have identified psoriasis-associated metabolites, findings are often limited by sample sizes and lack validation. Objectives: We aimed to identify circulating metabolites associated with psoriasis, including cutaneous activity, severity, and psoriatic arthritis. Further, we investigated whether the signature was disease-specific compared to other immune-mediated inflammatory diseases (IMIDs). Methods: We performed a cross-sectional analysis of 270,848 White/European individuals from the UK Biobank (n=253,924) and HUNT (n=16,924). Both cohorts used nuclear magnetic resonance spectroscopy to quantify metabolite levels, covering lipoprotein fractions and subfractions, fatty acids, and small-molecular metabolites. For each metabolite, we performed multivariable linear regression adjusting for age, sex, BMI, smoking status, and use of lipid-lowering medications. Results: The metabolomic profile of psoriasis was largely consistent across cohorts. In the model adjusted for age and sex, 116 metabolic measures were associated with psoriasis in both cohorts. After full adjustment, only Glycoprotein acetyls (GlycA) remained associated with psoriasis (coefficient [95% CI]: 0.09 [0.07-0.11] in UK Biobank and 0.11 [0.06-0.17] in HUNT). Despite more substantial metabolic alterations in cutaneous-active psoriasis, GlycA was also elevated in HUNT participants reporting no active psoriasis rash (coefficient [95% CI]: 0.12 [0.04-0.20] in non-cutaneous-active and 0.11 [0.03-0.19] in cutaneous-active psoriasis). In HUNT, severe psoriasis exhibited more pronounced metabolic alterations compared to non-severe psoriasis. Across both cohorts, phenylalanine levels were highly elevated in psoriatic arthritis compared to cutaneous psoriasis (coefficient [95% CI]: 0.41 [0.20-0.62] in UK Biobank and 0.47 [0.28-0.67] in HUNT). All IMIDs showed elevated GlycA and reduced albumin, with milder changes in atopic dermatitis. Psoriasis in the HUNT cohort exhibited a distinct lipoprotein profile compared to other IMIDs. Conclusions: This large-scale, cross-cohort study confirms metabolic alterations in individuals with psoriasis and highlights elevated GlycA levels regardless of cutaneous activity. The distinct metabolomic profile of psoriasis relative to other IMIDs suggests a potentially unique systemic profile. These findings offer a foundation for advancing biomarker research and mechanistic studies for psoriasis.Weiterlesen

BackgroundPsoriatic arthritis (PsA) and juvenile PsA (jPsA) are chronic inflammatory diseases with similar features that differ by age and sequence of symptom onset. PsA and psoriasis (PsO) share comparable pathology across ages, with interleukin (IL)-23 as a key mediator. Prior to the recent US FDA approval of guselkumab for treatment of pediatric plaque PsO and active jPsA, no approved pediatric treatment selectively targeted IL-23 signaling. Guselkumab (a fully human, dual-acting, IL-23p19 subunit inhibitor) was shown to be safe and effective in adult PsO and PsA, with consistent clinical benefits and safety in pediatric PsO. As jPsA shares features, including clinical characteristics and pathogenesis, with PsO and PsA, findings were extrapolated to jPsA using a similar approach previously applied to support ustekinumab and golimumab use in jPsA, which served as precedents for these analyses with guselkumab.AimsThe aim of this study was to demonstrate the similarity of serum guselkumab concentrations, clinical response, and safety among children and adults with PsO and/or PsA in guselkumab randomized controlled trials.MethodsOne-year data from participants receiving guselkumab at Week (W)0, W4, then every 8 weeks in VOYAGE 1/2 (adult PsO; N = 1221), DISCOVER-1/-2 (adult PsA; N = 375), and PROTOSTAR (pediatric PsO; N = 92; n = 3 with concurrent jPsA) were included. Serum guselkumab concentrations, Investigator Global Assessment of clear/minimal (IGA 0/1) and Psoriasis Area and Severity Index (PASI) 75/90/100 response rates and safety outcomes were summarized.ResultsSerum guselkumab concentrations over 1 year were similar between pediatric (max median: 3.2 µg/mL) and adult PsO (3.7 µg/mL), adult PsO and PsA (4.2 µg/mL), and pediatric PsO and adult PsA. IGA 0/1 response rates at W16 were approximately similar in guselkumab-treated participants with pediatric PsO (66%), adult PsO (84%), and adult PsA (77%). W16 PASI 75/90/100 response rates were comparable across guselkumab-treated participants with pediatric PsO without jPsA (PASI 75: 77%; PASI 90: 56%; PASI 100: 33%), pediatric PsO with jPsA (1 of 2 participants achieved all PASI improvement levels), and adult PsA (77%; 55%; 22%). Guselkumab safety outcomes were similar across ages and diseases.ConclusionComparable pharmacokinetic and clinical findings with guselkumab in children with PsO (3 with concurrent jPsA) and adults with PsO and PsA support the extrapolation of efficacy and safety data from adults to children with jPsA, supporting guselkumab use in jPsA.Clinical trials registrationThe clinical trials included in this analysis are registered at www.Clinicaltrialsgov with the identifiers: NCT02207231 (VOYAGE 1), NCT02207244 (VOYAGE 2), NCT03162796 (DISCOVER-1), NCT03158285 (DISCOVER-2), and NCT03451851 (PROTOSTAR).Weiterlesen

ObjectiveTo investigate the distribution characteristics of peripheral blood lymphocyte subsets in elderly psoriasis patients and analyze the interactions between immunosenescence and psoriasis and their impact on immune cell subpopulations.MethodsThis cross-sectional study enrolled 318 psoriasis patients and 167 healthy controls, stratified by age into elderly (≥ 65 years) and non-elderly (18-64 years) groups. Peripheral blood lymphocyte subsets, including CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and NK cells, were analyzed using four-color flow cytometry. Generalized linear models were employed to analyze associations between PASI scores and lymphocyte subsets, and correlation network analysis was constructed to evaluate interaction patterns among immune cell populations.ResultsThe elderly psoriasis group demonstrated significantly reduced CD8+ T cell percentage compared to controls (24.52% vs. 28.62%, P < 0.001), accompanied by an elevated Th/Ts ratio (1.57 vs. 1.27, P < 0.001) and significantly increased NK cell percentage and absolute count. Generalized linear modeling revealed a significant negative interaction effect between psoriasis and age on CD8+ T cell percentage (β = -3.979, P = 0.019), while the Th/Ts ratio exhibited a significant positive interaction effect (β = 0.230, P = 0.010). B cell absolute count showed a positive correlation with PASI score (r = 0.180, P = 0.001), with this correlation being more pronounced in elderly patients (r = 0.308, P = 0.014). Network analysis demonstrated reduced connectivity density among immune cell subpopulations in elderly patients.ConclusionsElderly psoriasis patients exhibit age-related alterations in peripheral blood lymphocyte subset distribution, characterized by decreased CD8+ T cells, elevated Th/Ts ratio, and increased NK cells. B cells may serve as potential biomarkers for assessing disease severity in elderly psoriasis patients.Weiterlesen

Background: Managing psoriasis in patients with a history of lymphoma presents a unique clinical challenge. Psoriasis is associated with significant comorbidities such as cardiovascular disease and inflammatory arthritis, making optimal treatment vital. Systemic treatments like biologic agents may help mitigate these sequelae of systemic inflammation. However, concerns about immunosuppression in the context of lymphoma recurrence and progression complicate therapeutic decisions. Purpose: This review aims to examine the role of IL-12, IL-17, IL-23, and TNF-α in psoriasis and explores the safety of biologic therapies in this population, with a focus on impact on lymphoma recurrence and progression. Research Design: A narrative review of the current medical literature was conducted. Study Sample: The analysis synthesizes evidence from preclinical studies, clinical trials, post-marketing surveillance registries, retrospetive cohort studies, and case reports concerning the use of biologic agents in psoriasis. Data Collection: Relevant literature was identified an analyzed to compare the mechanisms of action, degree of immunosuppression, and available safety data of different biologic agent classes. Results: Based on current evidence, we propose that IL-17 and IL-23 inhibitors as preferred options due to their targeted mechanisms and favorable safety profiles. In contrast, TNF-α inhibitors are less favored due to their comparatively greater immunosuppressive effects and potential association with lymphoma risk. IL-12/23 inhibitors are questionable given their potential impact on tumor immunosurveillance. Conclusion: For psoriasis patients with a history of lymphoma, IL-17 and IL-23 inhibitors represent the most suitable biologic options, while TNF-α inhibitors and IL-12/23 inhibitors should be used with caution. Clinical data overall remains limited, however, as lymphoma patients are routinely excluded from clinical trials. Further research is needed to clarify long-term safety and optimize treatment strategies for this high-risk population.Weiterlesen