Drug survival of biologic therapies for palmoplantar pustulosis: A nationwide study.

BACKGROUND: Biological therapies have established efficacy in psoriasis vulgaris. However, palmoplantar pustulosis (PPP) has proven difficult to treat, and data on drug survival in these patients remain scarce. OBJECTIVE: To investigate drug survival of biological treatments in a nationwide cohort of patients with PPP. METHODS: We included all patients treated for PPP with a biologic from a prospective Danish nationwide registry between 2007 and 2019. Descriptive statistics were reported. Drug survival was calculated for all patients and specified for the most frequently used biologics. Drug survival was reported as median time to discontinuation. Kaplan-Meier plots were used to visualize drug survival. Trajectories of Dermatology Life Quality Index (DLQI) scores were plotted by interpolating between the different visits with a dermatologist for each treatment course. RESULTS: We identified 85 individual patients who received biological therapy for PPP across 194 treatment courses during follow-up. Of the included treatment courses, 151 (77.8%) were discontinued. The most frequent cause of discontinuation was ineffective response to treatment (54.3%), while 18.5% of courses were discontinued due to adverse events. The median drug survival across all therapies for PPP was 9.3 (Inter quartile range (IQR), 3.9-25.6) months. Ustekinumab demonstrated the longest median time to discontinuation of 14.6 (IQR, 9.1-51.8) months. The proportion of bio-naive patients in treatment at 12 months were according to drug 47.9% for adalimumab, 64.3% for ustekinumab and 40.0% for secukinumab. For bio-experienced, it was 58.2% adalimumab, 54.5% for ustekinumab and 51.4% for secukinumab. CONCLUSIONS: The treatment of PPP poses significant challenges, with limited drug survival observed across all therapies regardless of prior experience with biologics. Ustekinumab demonstrated the longest median drug survival. Notably, patients discontinuing therapy due to inefficacy exhibited higher DLQI scores, highlighting the importance of personalized treatment selection and timely consideration of therapy changes when inefficacy is established.

Ethnic endotypes in paediatric atopic dermatitis depend on immunotype, lipid composition and microbiota of the skin.

BACKGROUND: Atopic dermatitis (AD) endotypes differ with ethnicity. We examined the skin microbiota, cytokine and lipid profiles in Greenlandic Inuit and Danish children with AD. METHODS: Twenty-five Inuit children with AD and 25 Inuit control children were clinically examined and compared to previously collected data from 25 Danish children with AD. Skin tape strips and skin swabs were collected from lesional and non-lesional skin. Levels of cutaneous immune biomarkers, free sphingoid bases and their (glycosyl)ceramides were analysed. Skin swabs were analysed with 16S rRNA and tuf gene for characterization of bacterial species communities. RESULTS: Bacterial ß-diversity was significantly different between Inuit and Danish AD skin, in both lesional (p < 0.001) and non-lesional (p < 0.001) AD skin, and there was a higher relative abundance of Staphylococcus aureus in Danish compared to Inuit lesional (53% vs. 8%, p < 0.01) and non-lesional skin (55% vs. 5%, p < 0.001). Danish AD children had a higher α-diversity than Inuit children in non-lesional (p < 0.05) but not in lesional skin. Significantly higher levels of type 2 immunity cytokine interleukin (IL)-4 (p < 0.05) and IL-5 (p < 0.01) were identified in Inuit compared to Danish AD children. In contrast, IL-33 (p < 0.01) was higher in Danish lesional and non-lesional AD skin. Higher levels of long-chain glucosylceramide (GlcCER)[S](d26:1) were found in lesional (p < 0.001) and non-lesional (p < 0.001) Inuit skin compared with Danish AD skin. NMF levels were similar in Inuit and Danish AD skin. CONCLUSION: Skin microbiota, cytokine and lipid composition differed significantly between Inuit and Danish children with AD and showed a stronger type 2 immune signature in Inuit children.

A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

Prevalence and characterization of treatment-refractory psoriasis and super-responders to biologic treatment: a nationwide study.

INTRODUCTION: Treatment with biologics often leads to clearance of psoriasis. However, some patients do repeatedly fail to respond and/or lose an achieved response (treatment refractory) to the biologic, whereas other patients achieve excellent response to one biologic and remain clear of psoriasis for several years (super-responders). OBJECTIVE: To identify and characterize patients with treatment refractory psoriasis and patients who are super-responders to biologic treatment. MATERIAL AND METHODS: Patients registered in DERMBIO between January 2007 and November 2019 were included. Patients were categorized as being treatment refractory if they had had treatment failure to ≥3 biologics targeting ≥2 different pathways. Super-responders were patients treated with their first biologic for minimum 5 years without an absolute psoriasis area and severity index (PASI) > 3 between 6 months and 5 years of treatment. All remaining patients from DERMBIO served as comparators. RESULTS: In total, 3280 patients were included with a mean age of 45.0 years. 1221 (37%) of the patients were females. Of the included patients, 214 (6.5%) were categorized as treatment refractory and 207 (6.3%) were categorized as super-responders. Treatment refractory patients had higher mean body weight (100.6 kg vs. 90.6 kg, P < 0.0001) and higher mean BMI (32.2 vs. 29.4, P < 0.0001) compared with the rest of patients in DERMBIO. Super-responders had higher socioeconomic status and fewer comorbidities compared with the comparator group (P < 0.0001). CONCLUSION: A small proportion of patients with psoriasis treated with biologics are either super-responders or treatment refractory. Treatment refractory patients have higher body weight, whereas super-responders have fewer comorbidities and higher socioeconomic status.

Atopic dermatitis among children and adolescents in the Arctic region - a systematic review and meta-analysis.

The prevalence of atopic dermatitis (AD) varies across the globe, and the clinical phenotype with racial background and ethnicity. AD in the Arctic region has only been scarcely studied. We performed a systematic review and meta-analysis to examine the prevalence, clinical manifestations and risk factors for AD among children and adolescents in the Arctic. Three medical databases PubMed, Embase and Web of Science were screened. All studies published between 1990 to 2020 with epidemiologic data on AD in children and adolescents in the Arctic region, were included. Data were extracted and a meta-analysis was performed to obtain pooled proportions and incidences with 95% confidence intervals (CI). We identified 21 studies from 8 different Arctic regions with 31 403 participants. The cumulative incidence of AD was 23% (95% CI 20-26) and 1-year prevalence was 19% (95% CI 15-25). The incidence of AD was higher in the Arctic parts of Scandinavia and lower in Greenland and Russia. Children of indigenous descent had a slightly lower incidence of AD (19%, 95% CI 13-26) compared to the overall population. The dominant phenotype of AD was mild to moderate flexural dermatitis with facial involvement. Asthma and allergic rhinitis were common and observed in 20-30% of children with AD. In conclusion, AD is highly prevalent in the Arctic, but varies between regions and races. Indigenous children living in less urbanized countries appear to have a slightly lower risk of AD. Future studies should confirm this and examine whether this correlation relates to behavioural differences or genetic signature.

Association between hospital-diagnosed atopic dermatitis and psychiatric disorders and medication use in childhood.

BACKGROUND: While adult atopic dermatitis (AD) is associated with anxiety and depression, and paediatric AD is linked to attention deficit hyperactivity disorder (ADHD), the relationship between AD in childhood and other psychiatric disorders is largely unknown. OBJECTIVES: To determine the relationship between AD and diagnosis and treatment of psychiatric disorders in children. METHODS: All Danish children born between 1 January 1995 and 31 December 2012 with a hospital diagnosis of AD (n = 14 283) were matched 1 : 10 with children without a hospital diagnosis of AD. Endpoints were psychotropic medication use, hospital diagnoses of depression, anxiety, ADHD, or self-harming behaviour, accidental/suicidal death, and consultation with a psychiatrist or psychologist. RESULTS: Significant associations were observed between hospital-diagnosed AD and antidepressant [adjusted hazard ratio (aHR) 1·19, 95% confidence interval (CI) 1·04-1·36], anxiolytic (aHR 1·72, 95% CI 1·57-1·90), and centrally acting sympathomimetic (aHR 1·29, 95% CI 1·18-1·42) medication use. Consultation with a psychiatrist (aHR 1·33, 95% CI 1·16-1·52) or psychologist (aHR 1·25, 95% CI 1·11-1·41) was also associated with AD. No association with a hospital diagnosis of depression (aHR 0·58, 95% CI 0·21-1·56), anxiety (aHR 1·47, 95% CI 0·98-2·22) or self-harming behaviour (aHR 0·88, 95% CI 0·27-2·88) was observed, but a diagnosis of ADHD (aHR 1·91, 95% CI 1·56-2·32) was significantly associated with AD. The absolute risks were generally low. CONCLUSIONS: The increased risk of treatment, but not of a hospital diagnosis of psychiatric disorders in children with hospital-diagnosed AD, suggests that psychiatric issues in children with AD could be of a transient, reversible or mild-moderate nature.

Disease severity and trigger factors in Danish children with atopic dermatitis: a nationwide study.

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronically relapsing inflammatory skin disease of childhood. However, little is known about self-reported trigger factors, impact on daily life and factors associated with AD severity. METHODS: A nationwide questionnaire study of children in Denmark with hospital-diagnosed AD in the time period 2014-2018. The web-based questionnaire was completed by the legal parents. AD severity was assessed using Patient-Oriented Eczema Measure (POEM) tool. RESULTS: Of 3438 invited parents, 1343 (39%) completed the questionnaire. Factors associated with severe AD were onset during the first 6 months of life, onset of AD on multiple body regions, a history of hay fever, female sex and low maternal educational level. Staying home from daycare or school due to AD, concentration problems and sleep disturbances in the child were more frequently reported by parents to children with severe AD. Overall, 90% reported at least one AD trigger factor, and all were more frequently reported in children with severe AD. The three most commonly reported trigger factors were cold weather (51.9%), chlorinated water (35.7%) and warm weather (30.2%). CONCLUSIONS: We identified factors associated with severe AD in childhood, the impact on daily life, as well as the most common self-reported triggers of AD. These findings may be valuable in clinical practice to inform about prognosis and educate families about trigger avoidance.

Clinical characteristics including cardiovascular and metabolic risk factors in adolescents with psoriasis.

BACKGROUND: Clinical studies on psoriasis in adolescents have mainly been performed in patients with severe psoriasis. Population-based studies of clinical characteristics and risk factors for later cardiovascular and metabolic disease in children and adolescents are lacking. OBJECTIVES: To examine the clinical characteristics of adolescents with psoriasis nested in a general population cohort. Furthermore, to investigate cardiovascular and metabolic risk factors in the adolescents with psoriasis compared to parentally predisposed and non-predisposed adolescents without psoriasis from the same birth cohort. METHODS: We identified adolescents with and without psoriasis using a nationwide general population birth cohort in Denmark. A clinical examination included skin inspection and scoring of psoriasis severity, completion of a questionnaire on psoriasis and comorbidities, physical measurements, and blood sampling. Participants also completed self-administered questionnaires on quality of life and mental health. RESULTS: We included 81 adolescents with psoriasis and 234 controls (110 with genetic predisposition for psoriasis and 124 without predisposition). Median age was 15.6 (13.5-18.5) years, and in those with active psoriasis, median Psoriasis Area and Severity Index score was 1.2 (0.1-11.4). The scalp was the most common site of psoriasis, both at debut and at time of examination. Diaper rash in infancy was more frequent in the psoriasis group. No significant differences regarding quality of life, anxiety and depression were found. More adolescents with psoriasis were obese (8.6% vs. 1.7%, P = 0.008), and physical measures of abdominal obesity were also significantly higher. HbA1c was significantly higher (31.55 vs. 30.81 mmol/mol, P = 0.048), while no differences were found for blood pressure, lipids or high-sensitivity C-reactive protein. In a subgroup analysis, this was evident in the non-predisposed psoriasis-free controls only. CONCLUSIONS: Overall, adolescents with psoriasis from this general population had mild disease. Still, early markers of cardiovascular and metabolic disease were elevated.

Development and preliminary validation of the Adolescent Psoriasis Quality of Life instrument: a disease-specific measure of quality of life in adolescents with psoriasis.

BACKGROUND: No age-appropriate and disease-specific instrument currently exists to measure health-related quality of life in adolescents with psoriasis (patients aged 12-17 years). OBJECTIVES: To develop and provide preliminary validation of the Adolescent Psoriasis Quality of Life instrument. METHODS: Qualitative interviews with adolescents with psoriasis, parents of adolescents with psoriasis, and healthcare professionals informed the development of an initial item pool for the instrument, which was subsequently refined through cognitive interviews. Finally, data from an independent sample of adolescents with psoriasis (n = 50) were used for item reduction, scale construction and initial validation, using a combination of techniques from classical test theory and Rasch modelling. RESULTS: Rich qualitative data concerning health-related quality of life in adolescents with psoriasis (from 18 adolescents, 14 parents and four healthcare professionals), combined with cognitive interview testing (n = 12), resulted in a 41-item draft version. Item reduction led to the final version, a 17-item instrument consisting of two subscales showing good fit to their respective Rasch models: psychosocial impact (12 items) and the impact of physical symptoms and treatment (five items). All a priori stated hypotheses regarding construct validity were supported. Both subscales and the total scale showed acceptable test-retest reliabilities (intraclass correlations 0·97, 0·89 and 0·96) and internal consistencies (Cronbach's α 0·94, 0·81 and 0·95). CONCLUSIONS: The preliminary form of the Adolescent Psoriasis Quality of Life instrument shows promising psychometric properties. It can be used in daily clinical practice and research to support a patient-centred approach and inform treatment planning. What's already known about this topic? Health-related quality of life (HRQoL) instruments should be targeted towards narrowly defined age groups, as life contexts of children, adolescents and adults may differ substantially. Dermatology-specific instruments have been used to measure HRQoL in adolescents with psoriasis, but it is not known whether these instruments accurately capture all relevant HRQoL aspects in adolescent psoriasis. Age-appropriate and psoriasis-specific instruments may be more sensitive for HRQoL issues experienced by this unique group. What does this study add? The Adolescent Psoriasis Quality of Life instrument represents the first age-appropriate and disease-specific instrument for measuring HRQoL in adolescents (12-17 years old) with psoriasis. It is intended for use in daily clinical practice to support dermatologists and other healthcare professionals in providing optimal care for adolescents with psoriasis.

Adverse events with IL-17 and IL-23 inhibitors for psoriasis and psoriatic arthritis: a systematic review and meta-analysis of phase III studies.

Biologics targeting interleukin (IL)-17 and IL-23 are generally well-tolerated and considered safe, though adverse events are seen more often compared with placebo. The objectives of this systematic review and meta-analysis were to assess the prevalence of adverse events in patients with psoriasis or psoriatic arthritis with any adverse events after 12, 16, 24 and 52 weeks of treatment with IL-17 or IL-23 inhibitors. Two independent authors searched the databases PubMed and EMBASE for studies reporting on adverse events in phase 3 trials of IL-17 and IL-23 inhibitors for patients with psoriasis and psoriatic arthritis. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data synthesis was performed using a random-effects model. In total, 44 publications (43 studies) were included in the analyses. The proportion of patients with any adverse events for all treatments pooled were 0.57 [95% confidence interval (CI): 0.55-0.59] after 12 weeks, 0.52 (95% CI: 0.49-0.55) after 16 weeks, 0.72 (95% CI: 0.66-0.78) after 24 weeks and 0.81 (95% CI: 0.76-0.86) after 52 weeks. Across therapies, the most prevalent AEs were infections, nasopharyngitis and headache. For ixekizumab one of the most prevalent AEs was injection site reactions, reported in 15.7% of the patients after 52 weeks. Overall, IL-17 and IL-23 inhibitors appear to be well-tolerated with good safety profiles. Our findings may aid the clinical decision making when choosing the most appropriate therapy for patients with moderate-to-severe psoriasis.

Cutaneous Lymphomas.

Primary cutaneous lymphomas are the second most common form of extra-nodal lymphomas. They have special characteristics compared with other lymphomas. They are most frequently of T-cell origin and they generally have a much more indolent course than lymphomas of similar histology in other locations. Mycosis fungoides is the most common type of cutaneous lymphoma. Primary cutaneous lymphomas remain confined to the skin for a long time. Skin-directed therapies are the main treatments; systemic treatments are not very effective for the skin lesions. Skin-directed therapies used for the early and thin lesions are topical corticosteroids, phototherapy and topical retinoids and, for the more widespread or thick lesions, topical nitrogen mustard and radiation. Radiation therapy is highly effective and is indicated in virtually all cases of localised disease. Radiation therapy may be given to the whole skin surface, so-called total skin electron beam therapy. However, if the disease spreads to other organs, systemic treatments are indicated, often combined with skin-directed therapies. Conventional cytotoxic therapy is less effective in cutaneous lymphomas. The commonly used therapies, such as interferon, enhanced anti-tumour immunity and the recent advances in immune therapies may improve our treatments for cutaneous lymphomas.

Quality of life and contact with healthcare systems among patients with psoriasis and psoriatic arthritis: results from the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP).

Psoriasis (skin psoriasis, PsO) is a chronic inflammatory condition. In about one-third of cases, the joints are affected (psoriatic arthritis, PsA). Both conditions, especially PsA, profoundly impact patients' health-related quality of life (HRQoL). To describe the impact of psoriasis on HRQoL and patients' contact with the healthcare system in Sweden, Denmark, and Norway, the NORdic PAtient survey of Psoriasis and Psoriatic arthritis (NORPAPP) asked 22,050 adults randomly selected in Sweden, Denmark and Norway if they had psoriasis. 1264 individuals who reported physician-diagnosed PsO/PsA were invited to the full survey; 1221 responded (74.6% diagnosed with PsO alone; 25.4% with PsA ± PsO). Respondents with PsA most frequently consulted a rheumatologist; however, 14.3% had never seen a rheumatologist. Respondents with PsO alone most frequently consulted a general practitioner and 10.7% had never seen a dermatologist (although those with severe symptoms visited dermatologists more often). Negative impacts on HRQoL were reported by 38.1% of respondents with PsO [mostly limitations on clothing (22.6%), sleep disorders (16%), and depression/anxiety (16%)] and by 73% of respondents with PsA [mostly limitations on clothing (41.8%), sports/leisure (44.0%), or daily routine (45.1%) and sleeping disorders]. Absence from work/education was more common with PsA ± PsO (51.9%) than PsO alone (15.1%). In this survey in Sweden, Denmark, and Norway, the impact of psoriasis on the respondents' HRQoL was profound and was greater for PsA than for PsO, as was sickness absence. Sleeping disorders and depression were common and should not be overlooked.