Purpose:Psoriasis extends beyond skin manifestations and significantly impacts patients' psychological health, social interactions, and daily functioning. The main objective was to assess the 2-year effect of tildrakizumab, an interleukin-23p19 inhibitor, on the skin, the psychological well-being and the health-related quality of life (HRQoL) of people with psoriatic disease in real-world. Patients and Methods:The POSITIVE study is a 24-month, prospective observational multinational study enrolling adults with moderate-to-severe plaque psoriasis treated with tildrakizumab according to clinical practice. Outcome measurements included the 5-item WHO Well-being Index (WHO-5), Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index-Relevant (DLQI-R). Results:785 patients were included. The mean (95% CI) WHO-5 score increased from 53.7 (52.2, 55.3) at baseline to 63.2 (61.5, 64.8) at W16 and continued improving over time: 65.9 (64.0, 67.9) at W52 and 70.4 (68.1, 72.7) at W104. The mean (95% CI) PASI decreased from 12.9 (12.3, 13.5) at baseline to 2.4 (2.2, 2.7) at W16 and was maintained until W104 [1.3 (1.1, 1.5)]. At W104, 87.9/79.0/65.1% of patients maintained PASI ≤3/≤2/≤1. Drug survival due to lack of effectiveness or adverse events (AE) was 87.8% and 96.3% after 2 years. The mean (95% CI) DLQI-R score decreased from 12.0 (11.4, 12.6) at baseline to 3.1 (2.6, 3.6) W52 and 2.1 (1.7, 2.5) at W104. At the final analysis, 11.1% of patients had ≥1 related AE. Conclusion:Treatment with tildrakizumab delivered sustained and holistic long-term health for moderate to severe psoriasis over 2 years by consistently improving patients' psychological well-being, life and clinical outcomes with a favourable safety profile. ClinicalTrialsgov ID:NCT04823247.

BACKGROUND:Little is known about the clinical characteristics, diagnostic delay and treatment survival in patients with palmoplantar pustulosis (PPP). OBJECTIVES:To analyse the survival rates of patients with PPP in Austria treated with phototherapy, conventional systemic therapies and biologics. METHODS:This was a retrospective study using data from the Psoriasis Registry Austria (PsoRA). The analysis included data collected between 16 May 1997 and 11 April 2024 from patients with PPP. RESULTS:We included data from 190 patients who underwent 397 treatments. Fifty-four per cent of patients (n = 37/69) were initially misdiagnosed as having eczema with a mean (SD) diagnostic delay of 2.8 (4.8) years. Patients were predominantly women (n = 141/190; 74.2%) and smoked (n = 76/98; 78%). Patients were treated with biologics (n = 198/397; 49.9%), phototherapy (n = 100/397; 25.2%) and conventional systemic therapies (n = 99/397; 24.9%). Median survival time for all treatments was 0.6 years [95% confidence interval (CI) 0.5-0.8], with patients on ustekinumab having the longest median survival time of 2.7 years (95% CI 2.3-upper limit not reached), surpassing all other therapies. This superiority disappeared after interleukin (IL)-23p19 inhibitors were introduced in Austria. Compared with biologics, conventional systemic treatments [hazard ratio (HR) 2.17; P < 0.001] and phototherapy (HR 4.43; P < 0.001) were associated with a significantly higher risk of treatment discontinuation. In the overall cohort, disease durations of ≥ 2 to < 10 years (HR 0.66; P = 0.05) and ≥ 10 years (HR 0.59; P = 0.004) significantly reduced the risk of treatment discontinuation, while concomitant plaque psoriasis significantly increased the risk of treatment discontinuation (HR 1.43; P = 0.05). In the biologic cohort, concomitant arthritis (HR 2.11; P = 0.002) and the presence of one comorbid disease (HR 2.34; P = 0.03) increased the risk of treatment discontinuation. Furthermore, sex, age at disease onset and smoking did not influence the risk of treatment discontinuation. CONCLUSIONS:Our findings suggest that more than half of patients with PPP experience a diagnostic delay of several years due to an initial misdiagnosis. Patients on ustekinumab (IL-12/23p40 inhibitor) had the longest treatment survival, although its superiority diminished with the introduction of IL-23p19 inhibitors. Finally, shorter disease duration and concomitant plaque psoriasis is a general risk factor for treatment discontinuation, while the presence of a comorbidity and concomitant psoriatic arthritis are risk factors for discontinuing biologics.

Abstract Moderate-to-severe psoriasis can profoundly impact mental health, and a delay between physical and psychological improvement in patients with skin disease has been described as ­‘psycholag’. However, this phenomenon has been barely explored in the context of biologic therapies in psoriasis. We evaluated whether patients with moderate-to-severe psoriasis treated with tildrakizumab experience psycholag by comparing improvements in skin vs. psychological wellbeing during 104 weeks of treatment. POSITIVE is a 24-month phase IV multicountry observational study in adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab in a real-world setting. The study is funded by Almirall. Psoriasis Area and Severity Index (PASI) and WHO-5 Well-Being Index were used to assess clinical effectiveness and psychological wellbeing, respectively. A WHO-5 score ≥ 64 (European population average) indicates psychological wellbeing control; PASI ≤ 2 indicates skin control. The study included 171 patients with WHO-5 < 64 and PASI > 2 at baseline. At week 16, 56 patients (32.7%) achieved both psychological wellbeing and skin control: WHO-5 increased from 45.9 to 75.4 and PASI decreased from 14.5 to 0.7. Notably, 51 patients (29.8%) achieved similar skin control (PASI change from 12.4 to 0.9) but still had impaired psychological wellbeing (WHO-5 change from 37.1 to 44.6). Nineteen (37%) of these experienced psycholag within the first 52 weeks: 13 had improved psychological wellbeing by week 28 (WHO-5 score 72.0) and 6 by week 52 (WHO-5 score 76.7). Over 52 weeks, skin control was maintained in 27 patients, while psychological wellbeing showed only slight improvement (WHO-5 score 40.1). The POSITIVE study demonstrates that tildrakizumab improves both physical symptoms and psychological wellbeing within 16 weeks in most patients. However, psycholag was exhibited by some patients. When evaluating treatment success in skin disease, psychological parameters should be measured alongside physical outcomes to enhance people-centred healthcare.

Background:Psoriasis and mental health are closely intertwined; however, certain aspects remain underexplored. Thus, continued research on this topic is important to deepen our understanding. Objectives:To explore the mental health of individuals with psoriasis - specifically depressive symptoms, mental functioning, stress symptoms and coping strategies - and to find associations with physical manifestations of psoriasis. Methods:A cross-sectional sample of 214 individuals with psoriasis (107 with illness duration >16 years and 107 with illness duration ≤16 years; cut-off: median) completed the Beck Depression Inventory-II, the SF-12 measuring mental and physical functioning, and the Stress and Coping Inventory. Additionally, the Psoriasis Area and Severity Index (PASI) was assessed. The study was conducted during the COVID-19 pandemic. Results:Individuals with psoriasis reported worse mental and physical health than the general population (norm sample of SF-12) but did not differ significantly from each other. While individuals with illness duration >16 years had lower psoriasis severity than those with illness duration ≤16 years, mean PASI scores indicated low illness severity overall. PASI scores did not show significant correlations with mental health inventories in either group. Conclusions:Individuals with psoriasis reported lower mental health during the COVID-19 pandemic than a healthy, prepandemic norm sample, independent of psoriasis severity. Age and illness duration seem to facilitate coping with the disease. Nevertheless, individuals with psoriasis are in need of continued mental health support, regardless of illness duration.

BACKGROUND:Psoriatic disease is a lifelong chronic illness for which there is no cure. It is well established that psoriasis leads to a major impairment of health-related quality-of-life and wellbeing. Most people with psoriasis live together with partners, bringing along a major burden for them. The FamilyPso was created to measure this burden in psoriasis. OBJECTIVE:The aim of the FamilyPso international study was to validate this tool and to show feasibility for the use of the FamilyPso across multiple countries. METHODS:A prospective cohort study was conducted in 11 centers in Austria, Canada, Germany, Italy, Spain, and Turkey. The factor structure of the FamiliyPso was examined by confirmatory factor analysis (CFA) including tests of measurement invariance for gender and language. Subgroups (e.g., countries and gender) were tested for significant differences, and the relationship between the severity of illness and FamilyPso scores was tested for differences between countries using a mixed regression model. Descriptive statistics for items and scores are presented herein. RESULTS:The cohort consisted of 556 people with psoriasis and their partners. Patients agreed that their partners would answer the questionnaire in their absence and return the forms to the centers. The mean age of patients and partners was 51 years. Psoriasis severity was mild in 57.6%, moderate in 31.5%, and severe in 10.9% of cases, and 91.3% received treatment. The results of the CFA confirmed the original factor structure with minor modifications. Self-assessed high severity of psoriasis was a predictor for a higher burden in 4/5 FamilyPso domains. There was an increased burden to partners related to the severity of psoriasis particularly in the domain "general emotional strain," including items such as a "feeling of helplessness." The results of the study showed that the FamilyPso could assess the burden of partners of people with psoriasis and can be used across different countries. CONCLUSIONS:The data can improve management of psoriatic disease and should be considered in shared decision-making.

Background:Little is known about treatment survival in patients with plaque psoriasis who have received phototherapy. Objectives:to analyse treatment survival in patients with plaque psoriasis who had received photother-apy, irrespective of the number of sessions and type of phototherapy, and to identify factors that influence the risk of treatment discontinuation. Methods:Data from the Psoriasis Registry Austria and the phototherapy registry of the Centre of Phototherapy at the Department of Dermatology and Venereology, Medical University of Graz, were retrospectively analysed using Kaplan-Meier curves (logrank test) and a Cox (proportional hazards) regression analysis, irrespective of the number of phototherapy sessions or type of phototherapy. Results:The analysis revealed an overall treatment survival rate of 70% and 66% after 1 and 3 years, respectively, with a median treatment survival of 5.5 years. However, treatment survival rates have significantly decreased compared with the rates reported in the prebiologic era [hazard ratio (HR) 1.98, P < 0.001]. While female sex did not influence overall treatment survival (HR 0.87, P = 0.28), the risk of treatment discontinuation was significantly lower in women aged ≥ 60 years (HR 0.49, P = 0.009). Moreover, patients with arthritis had an increased risk of treatment discontinuation (HR 1.69, P = 0.003). The involvement of high-impact body areas (including scalp, nail, or inverse and/or genital body areas) did not alter treatment survival; however, palmar and/or plantar involvement increased the risk of treatment discontinuation (HR 1.48, P = 0.006), especially in men (HR 2.19, P < 0.001). No significant differences in the treatment survival of phototherapy in patients were observed regarding the duration of the psoriasis. Conclusion:Male patients with psoriasis with palmar and/or plantar involvement have the highest risk of treatment discontinuation, whereas women aged ≥ 60 years at treatment start have the lowest risk. Therefore, early treatment escalation should be considered in men with palmar and/or plantar involvement and treatment-resistance disease forms. However, the current treatment survival rates reported for patients with psoriasis treated with phototherapy (median survival 30 months) are similar to the treatment survival rates reported for patients receiving tumour necrosis factor inhibitors.

Purpose:Psoriasis profoundly impairs patients' social, emotional, and physical condition, impacting on their overall well-being. Tildrakizumab is an interleukin-23p19 inhibitor labelled for the treatment of moderate-to-severe plaque psoriasis. The main objective of this study was to assess the effect of tildrakizumab on the overall well-being of people with psoriasis. Effectiveness, quality of life (QoL), symptomatology, treatment satisfaction, and the impact of psoriasis on the patients' partners were also evaluated. Patients and Methods:POSITIVE is a 24-month observational study in adults with moderate-to-severe psoriasis treated with tildrakizumab in a real-world setting (ClinicalTrials.gov ID: NCT04823247). Outcome measurements included the 5-item WHO Well-being Index (WHO-5), Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index-Relevant (DLQI-R), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and FamilyPso. We report 52-week (W52) interim data (N = 400; observed cases). Results:Mean ± 95% CI WHO-5 score increased from 53.8 ± 2.2 at baseline to 66.0 ± 2.3/65.7 ± 2.7 at W28/W52 (p < 0.0001, both). Mean ± 95% CI PASI decreased from 13.1 ± 0.8 at baseline to 1.7 ± 0.3/1.5 ± 0.3 at W28/W52 (p < 0.0001, both). At W28 and W52, 85.8%/54.8% and 88.4%/56.8% of patients achieved PASI ≤ 3/≤ 1. Mean ± 95% CI DLQI-R score decreased from 12.6 ± 0.8 at baseline to 3.3 ± 0.6/3.1 ± 0.6 at W28/W52 (p < 0.0001, both). At W52, mean ± 95% CI TSQM-9 domain scores were 77.4 ± 3.2 for effectiveness, 81.5 ± 2.6 convenience, and 81.1 ± 2.6 global satisfaction. Mean ± 95% CI total FamilyPso decreased from 1.3 ± 0.1 at baseline to 0.7 ± 0.2 at W52 (p < 0.0001). At the point of this analysis, 24.0% of patients had ≥1 adverse event (AE). Only one patient discontinued due to a treatment-related AE. Conclusion:Tildrakizumab successfully contributes to value-based long-term health care for moderate-to-severe psoriasis by increasing patient wellbeing, QoL and clinical outcomes while showing very good safety and tolerability.

BACKGROUND:The proinflammatory cytokine IL-17 is known to play an important role in psoriasis pathogenesis, but little is known about its regulation in psoriasis or after treatment. OBJECTIVE:Aiming to investigate the role of IL-17 regulation in the resolution of psoriasis, we analyzed biopsy samples from patients with plaque psoriasis, including non-lesional and lesional skin at baseline and after anti-IL-17 and -IL-23 antibody, topical dithranol or UVB treatment as well as skin from healthy donors. METHODS:Skin biopsy samples were analyzed using immunostaining, RNA sequencing and in situ mRNA detection. In addition, we investigated IL-17 concentration of primary human skin mast cell supernatants after stimulation with the pro-inflammatory cytokines TNFα, IL-22, IL-23 and IFNγ. RESULTS:A high number of IL-17A+ mast cells persisted in resolved lesions after treatment and correlated inversely with the time span in remission. IL-17A+ mast cells were found in T cell-rich areas and near resident memory T cells in active and resolved lesions. CIBERSORTx deconvolution of RNA-seq data of active and dithranol-treated psoriasis lesions showed that activated mast cells were increased in psoriatic skin but returned to normal levels after treatment. Primary skin mast cells responded with an increased release of IL-17A after stimulation with the pro-inflammatory cytokines and in situ mRNA detection revealed positive signals for IL17A, IL17F and RORC in mast cells. CONCLUSION:Thus, together with T cells, mast cells seem to be important players of the IL-23/IL17 axis underlying psoriasis pathogenesis and relevant for early disease recurrence.

Introduction Le psoriasis est une maladie chronique qui affecte profondément les composantes sociales, émotionnelle, fonctionnelle et physique de la qualité de vie des patients, ce qui a un impact sur leur bien-être général. Le prurit, la douleur cutanée, articulaire et la fatigue sont des symptômes importants chez les patients atteints de psoriasis. Le tildrakizumab est un inhibiteur de l’interleukine-23p19 indiqué dans le traitement du psoriasis en plaques modéré à sévère et dont l’efficacité et la sécurité à long terme ont été démontrées. Matériel et méthodes POSITIVE est une étude multinationale observationnelle de phase IV, d’une durée de 24 mois, menée auprès de patients adultes atteints de psoriasis en plaques modéré à sévère et traités par tildrakizumab. Elle étudie le bien-être rapporté par les patients utilisant le tildrakizumab. Les résultats de cette analyse comprenaient une échelle numérique (NRS) d’évaluation des démangeaisons, de la douleur, des douleurs articulaires et de la fatigue en 11 niveaux, allant de 0 à 10 (10=pires symptômes). Résultats Le score NRS moyen de prurit±IC à 95 % est passé de 5,7±0,3 à l’inclusion à 2,2±0,3 à la semaine 16, à 2,1±0,3 à la semaine 28 et à 2,4±0,4 à la semaine 52 (p<0,0001, pour toutes les analyses). Le score NRS moyen de douleur±IC à 95 % s’est amélioré de 4,1±0,3 à l’inclusion à 1,5±0,3 à la semaine 16, à 1,4±0,3 à la semaine 28, et à 1,2±0,3 à la semaine 52 (p<0,0001, pour toutes les analyses). Le score NRS moyen de douleur articulaire±IC à 95 % s’est amélioré de 2,5±0,3 à l’inclusion à 1,6±0,3 à la semaine 16, à 1,5±0,3 à la semaine 28, et à 1,4±0,3 à la semaine 52 (p<0,0001, pour toutes les analyses). Le score NRS moyen de fatigue±IC à 95 % s’est amélioré de 3,8±0,3 à l’inclusion à 1,9±0,3 à la semaine 16, à 1,8±0,3 à la semaine 28, et à 1,9±0,3 à la semaine 52 (p<0,0001, pour toutes les analyses). À la semaine 28 et à la semaine 52, respectivement, 69,3 %/74,0 %/52,1 %/65,6 % et 64,1 %/83,1 %/56,0 %/60,0 % des patients ayant à l’inclusion un score NRS de démangeaison/douleur/douleur articulaire/fatigue ≥4 ont obtenu une réduction de ≥4 points de leur score NRS respectif. Discussion Dans un contexte de vie réelle, le tildrakizumab a amélioré rapidement et de manière significative certains symptômes contraignants rapportés par les patients atteints de psoriasis en plaques modéré à sévère après 16 semaines de traitement. Cette amélioration s’est maintenue jusqu’à la semaine 28 puis jusqu’à la semaine 52. Conclusion Le fardeau de la maladie psoriasique est important et d’autant plus lourd lorsque certains symptômes sont associés comme le prurit, la douleur, la douleur articulaire et la fatigue. La diminution de ces symptômes voire leur disparition par le tildrakizumab a été observée rapidement puis maintenue pendant 52 semaines.