Search

Background Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. Objectives To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Methods Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator’s Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. Results After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. Conclusions After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

Background Research has linked homelessness with an increased risk of skin conditions. However, representative studies of diagnosis-specific information on skin conditions in people experiencing homelessness are lacking. Objectives To examine the association between homelessness and diagnosed skin conditions, prescribed medication and type of ­consultation. Methods This cohort study included data from the Danish nationwide health, social and administrative registers from 1 January 1999 to 31 December 2018. All people of Danish origin living in Denmark and aged at least 15 years at some point during the study period were included. Homelessness, measured by homeless shelter contacts, was the exposure. The outcome was any diagnosis of a skin disorder and specific skin disorders recorded in the Danish National Patient Register. Information on diagnostic consultation type (i.e. dermatological, nondermatological and emergency room) and dermatological prescriptions was studied. We estimated adjusted incidence rate ratio (aIRR) (adjusted for sex, age and calendar year) and cumulative incidence. Results In total, 5 054 238 individuals (50.6% female) were included in the study population, accounting for 73 477 258 person-years at risk, with a start mean (SD) age of 39.4 (21.1) years. Of the total number of individuals, 759 991 (15.0%) received a skin diagnosis and 38 071 (0.7%) experienced homelessness. A 2.31-times [95% confidence interval (CI) 2.25–2.36] higher IRR of any diagnosed skin condition was associated with homelessness, higher for nondermatological and emergency room consultations. Homelessness was associated with a reduced IRR of a skin neoplasm diagnosis (aIRR 0.76, 95% CI 0.71–8.82) compared with no homelessness. By the end of follow-up, 2.8% (95% CI 2.5–3.0) of individuals experiencing homelessness had a skin neoplasm diagnosis vs. 5.1% (95% CI 4.9–5.3) of individuals not experiencing homelessness. Five or more shelter contacts during the first year from first contact was associated with the highest aIRR of any diagnosed skin condition (7.33, 95% CI 5.57–9.65) compared with no contacts. Conclusions Individuals experiencing homelessness have high rates of most diagnosed skin conditions, but a lower occurrence of skin cancer diagnosis. Diagnostic and medical patterns for skin disorders differed clearly between people experiencing homelessness and individuals without these experiences. The time after first homeless shelter contact is an important window of opportunity for mitigating and preventing skin disorders.

Background Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Brazil and Chile are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. Objectives In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult patients with psoriasis in Brazil and Chile. Methods A multicentre, cross-sectional Global Healthcare Study on Psoriasis was performed in Brazil and Chile in 2020. For each eligible adult patient with psoriasis, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), body surface area (BSA) score and the Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a χ2-test or Fisher’s exact test, where appropriate, for categorical variables. The median and interquartile range (IQR) was calculated for non-normal distributed data. Results A total of 1424 patients with psoriasis from 43 centres [27 centres in Brazil (n = 826) and 16 in Chile (n = 598)], were included with a mean (SD) age of 49.1 (16.3) and 49.2 (15.1) years, respectively. Unstratified analyses revealed that patients with psoriasis in Chile had more severe disease than those in Brazil [PASI 11.6 vs. 8.4 (P < 0.001) and BSA 14.7 vs. 12.0 (P = 0.003), respectively]. For patients with moderate-to-severe psoriasis, defined as PASI and/or BSA ≥ 10, systemic nonbiologic drugs were available (81.2% in Brazil and 65.3% in Chile, P ≤ 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (P = 0.01). Lack of availability and/or lack of insurance reimbursement for biologic drugs for patients with moderate-to-severe psoriasis was reported for 22.2% (50 of 225) in Brazil and 67.9% (148 of 218) in Chile (P < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00–14.25) in Brazil and 12.0 (IQR 5.00–19.00) in Chile (P = 0.007), as well as a median BSA of 7.0 (IQR 3.00–15.00) and 12.0 (IQR 5.00–22.50) (P = 0.002), and median DLQI of 11.0 (6.00–15.00) and 21.0 (6.50–25.00) (P = 0.007), respectively. Conclusions Chilean patients had significantly more severe psoriasis compared with Brazilian patients in our study. While nonbiologic treatments for moderate-to-severe psoriasis were available in both LA countries, there is a high need for improvement in access to more effective psoriasis treatments including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.

According to their parents, some children with aluminium contact allergy and vaccination granulomas may react to aluminium-containing foods by developing dermatitis, granuloma itch and subjective symptoms.To determine whether oral intake of aluminium-containing pancakes can cause adverse events and/or systemic contact dermatitis (SCD) in children with vaccination granulomas and aluminium contact allergy.A total of 15 children aged 3-9 years (mean age, 5 years) with vaccination granulomas and positive patch-test results to aluminium chloride hexahydrate 2%/10% pet. completed a 3-week blinded randomized controlled crossover oral aluminium/placebo provocation study with pancakes. Granuloma itch and other subjective symptoms were evaluated daily on a visual analogue scale (VAS). Dermatitis was evaluated by the primary investigator, and sleep patterns were tracked with an electronic device. Aluminium bioavailability was assessed by measuring aluminium excretion in the urine. The children served as their own controls with the placebo provocations.All 15 children completed the study. The mean VAS scores were slightly higher during aluminium provocations compared to placebo for granuloma itch (mean VAS, 1.5 vs 1.4, P = 0.6) but identical for other subjective symptoms (0.6 vs 0.6, P = 1). There were no differences in sleep patterns and no significant correlation between urinary aluminium excretion and symptom severity. Three children developed a symmetrical rash on the face or buttocks on day 4 of the aluminium provocations, but not during placebo provocations.No difference was found between oral aluminium intake and the occurrence of subjective symptoms and granuloma itch, but on a case-basis oral aluminium may be associated with the development of systemic contact dermatitis.

Background The epidemiology of atopic dermatitis (AD) in Greenland has been sparsely investigated. Aim To examine the point and overall prevalence, cumulative incidence at different ages, and associated risk factors for AD among children in Greenland. Methods Between 2019 and 2020, three towns in Greenland, representing 48% of the total population, were visited. A cross-sectional study was conducted, including children aged 0–7 years attending daycare centres. Parents completed a questionnaire with questions on AD and related risk factors. A diagnosis of AD was based on the UK Working Party’s criteria along with a clinical examination. Results In total, 839 children aged 0–7 years were included. The overall prevalence of AD was 35% according to physician’s diagnosis and assessment. The point prevalence was 28% and peaked among 1-year-old children (36%) and declined with age. The cumulative incidence at ages 1–6 years varied between 29% and 41% and was highest in 1-year-old children and showed a slight decline with increasing age. In the fully adjusted multivariate model, AD was associated with being of Inuit descent [odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1–2.8]; food allergy in the child (OR 3.6, 95% CI 2.3–5.6); ear infection in the child (OR 1.4, 95% CI 1.0–1.9); having a mother with a high educational level (OR 1.5, 95% CI 1.0–2.3); maternal atopy (OR 1.4, 95% CI 1.1–2.0); and paternal atopy (OR 2.0, 95% CI 1.5–2.8). No environmental risk factors were identified. Conclusion The overall prevalence of AD in children in Greenland is high and has likely increased over the past 20 years. The point prevalence was highest in the youngest children indicating early onset of disease. Inuit descent, family atopy predisposition and having a higher socioeconomic status (based on parental educational level and housing) increased the risk of AD. Insight into possible Inuit-specific genetic predisposition is needed.

Background Children with atopic dermatitis (AD) may have disturbed sleep, affected self-esteem and decreased quality of life, likely interfering with performance in school. Objectives To examine the association between hospital-managed paediatric AD, school performance and cognitive function. Methods In this cross-sectional study we linked data from the Danish national registers and identified three populations between 2001 and 2019. Population 1 comprised children with graduation grades registered from lower secondary school, population 2 comprised adolescents with registration of an upper secondary graduation mean, and population 3 comprised male conscripts with registration of an IQ test score. AD was defined as a hospital diagnostic code (inpatient or outpatient) prior to the exam or conscription date, and was stratified according to severity, activity and atopic comorbidity. Outcomes included graduation mean from lower and upper secondary school, special educational assistance in primary and lower secondary school, and IQ at conscription. Results In total, 770 611 (12 137 with AD), 394 193 (6261 with AD) and 366 182 (4539 with AD) children and adolescents were included in populations 1 (lower secondary graduation), 2 (upper secondary graduation) and 3 (conscription), respectively. In lower secondary school, children with severe AD had significantly lower overall, written and oral graduation grade means compared with children with mild AD: respectively, difference −0.29 [95% confidence interval (CI) −0.45 to −0.13, P < 0.001], difference −0.26 (95% CI −0.42 to −0.10, P = 0.0016) and difference −0.30 (95% CI −0.49 to −0.11, P = 0.0018). In upper secondary school, adolescents with AD performed similarly to their peers without AD. Young men with AD scored significantly lower IQ test means at conscription examination than male conscripts without AD: difference −0.60 (95% CI −0.87 to −0.32, P < 0.001). Conclusions AD, in particular when severe, is associated with lower school performance in childhood and IQ in young men, which can interfere with academic achievements in life. Optimization of treatment of children with AD and specific educational support to children with severe AD could be needed.

Occupational hand eczema is frequent in metalworkers. The contribution of metal allergies is poorly elucidated even though such exposures are common at the workplace. To estimate the prevalence of metal allergy to cobalt (Co), chromium (Cr) and nickel (Ni) in metalworkers and compare these to estimates from the European Surveillance System on Contact Allergies (ESSCA). Two authors independently searched PubMed for studies reporting on the prevalence of metal allergy in metalworkers. Proportion meta-analyses were performed to calculate the pooled proportions of metal allergy in metalworkers. In total, 29 studies (22 from Europe) were included yielding 5691 subjects for quantitative analysis. The pooled proportion (95% confidence interval) of Co, Cr and Ni in European metalworkers with dermatitis referred to patch test clinics was 8.2% (5.3%-11.7%), 8.0% (5.1%-11.4%), and 11.0% (7.3%-15.4%), respectively. The corresponding estimates for unselected metalworkers from workplace studies were 4.9% (2.4%-8.1%), 5.2% (1.0%-12.6%), and 7.6% (3.8%-12.6%), respectively. In comparison, the prevalence of metal allergy in 13 382 consecutive European males with dermatitis was 3.9% (3.6%-4.2%), 4.4% (4.1%-4.8%) and 6.7% (6.3%-7.0%) for Co, Cr and Ni, respectively. Data on sex, age, body piercings and atopic dermatitis in metalworkers with metal allergy was mostly lacking. Metal allergy to all three metals was significantly more common in European metalworkers with dermatitis attending patch test clinics as compared to ESSCA data, indicating a relationship to occupational exposures, however, confounders could not be accounted for.

BackgroundChronic hand eczema (CHE) significantly impacts quality of life. Published literature on pediatric CHE (P-CHE) in North America including knowledge on epidemiology and standard evaluation and management is limited.ObjectiveOur objective was to assess diagnostic practices when evaluating patients with P-CHE in the US and Canada, produce data on therapeutic agent prescribing practices for the disorder, and lay the foundation for future studies.MethodsWe surveyed pediatric dermatologists to collect data on clinician and patient population demographics, diagnostic methods, therapeutic agent selection, among other statistics. From June 2021 to January 2022, a survey was distributed to members of the Pediatric Dermatology Research Alliance (PeDRA).ResultsFifty PeDRA members responded stating that they would be interested in participating, and 21 surveys were completed. For patients with P-CHE, providers most often utilize the diagnoses of irritant contact dermatitis, allergic contact dermatitis, dyshidrotic hand eczema, and atopic dermatitis. Contact allergy patch testing and bacterial hand culture are the most used tests for workup. Nearly all utilize topical corticosteroids as first line therapy. Most responders report that they have treated fewer than six patients with systemic agents and prefer dupilumab as first-line systemic therapy.ConclusionsThis is the first characterization of P-CHE among pediatric dermatologists in the United States and Canada. This assessment may prove useful in designing further investigations including prospective studies of P-CHE epidemiology, morphology, nomenclature, and management.

Compliance with glove use and safe work practices are important factors in primary prevention of occupational hand eczema (OHE) in hairdressers.To assess the risk OHE and compliance with skin protective measures in hairdressers trained before and after implementation of a nationwide skin protection program in Danish hairdressing vocational schools in 2011.A repeated cross-sectional study was performed. A questionnaire was sent in 2009 and 2020. The Danish Labour Market Supplementary Pension Scheme provided information on yearly payments from the hairdressing profession.A response rate of 66.6% (305/460) was obtained in the 2009 survey and of 29.9% (363/1215) in the 2020 survey. The career time prevalence of OHE decreased from 42.8% to 29.0% (adjusted odds ratio 0.55 95% confidence interval [CI] 0.40-0.77) and the incidence rate of OHE decreased from 57.5 (95%CI 48.4-68.4) to 42.0 (95%CI 34.6-50.9) per 1000 person years (incidence rate ratio 0.73 [95%CI 0.56-0.95] between the two surveys). A statistically significant (P .05) increase in glove use when doing wet-work and when handling hair dyes, permanent wave solutions and bleaching products was observed in the 2020 compared to the 2009 survey.Our data suggest that skin protection training during apprenticeship reduces the risk of OHE in hairdressers. The lack of primary prevention of OHE in hairdressing vocational schools may be a missed opportunity in the prevention of the disease.

Background: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. Objectives: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. Methods: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). Results and conclusions: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

Phase 3 trials have assessed efficacy of abrocitinib versus placebo in moderate-to-severe atopic dermatitis, a common immunoinflammatory skin disease. This study assessed the efficacy and safety of abrocitinib versus dupilumab.This randomised, double-blind, double-dummy, active-controlled, parallel-treatment, phase 3 trial enrolled adults with moderate-to-severe atopic dermatitis who requir=ed systemic therapy or had inadequate response to topical medications. Participants were enrolled from 151 sites, located in Australia, Bulgaria, Canada, Chile, Finland, Germany, Hungary, Italy, Latvia, Poland, Slovakia, South Korea, Spain, Taiwan, and the USA. These participants were then randomly assigned (1:1) with block randomisation to receive oral abrocitinib (200 mg per day) or subcutaneous dupilumab (300 mg every 2 weeks) for 26 weeks. Participants were required to apply topical corticosteroids (medium or low potency), topical calcineurin inhibitors, or a topical phosphodiesterase 4 inhibitor to active lesion areas. Primary endpoints were response based on achieving a 4 point or higher improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 2 and a 90% or better improvement in Eczema Area and Severity Index (EASI-90) at week 4. Family-wise type 1 error was controlled via a sequential multiple-testing procedure (two sided, α=0·05). Randomly assigned participants who received at least one dose of study intervention were included in the efficacy and safety analysis sets. This trial was completed on July 13, 2021 (NCT04345367).Between June 11, 2020, and Dec 16, 2020, 940 patients were screened and 727 were enrolled (362 in the abrocitinib group and 365 in the dupilumab group). Compared with dupilumab, a larger proportion of patients treated with abrocitinib reached the primary outcomes, PP-NRS4 at week 2 (172 [48%] of 357, 95% CI 43·0-53·4 vs 93 [26%] of 364, 21·1-30·0; difference 22·6%, 15·8-29·5; p0·0001), and EASI-90 at week 4 (101 [29%] of 354, 23·8-33·2 vs 53 [15%] of 364, 10·9-18·2; difference 14·1%, 8·2-20·0; p0·0001). Treatment-emergent adverse events were reported by 268 (74%) of 362 patients treated with abrocitinib and by 239 (65%) of 365 patients treated with dupilumab. Two non-treatment-related deaths occurred in the abrocitinib group.Abrocitinib 200 mg per day was more efficacious than dupilumab in adults with moderate-to-severe atopic dermatitis on background topical therapy in inducing early reductions of itch and atopic dermatitis disease signs. Both treatments were well tolerated over 26 weeks.Pfizer.

What is this summary about? Atopic dermatitis (AD, also called atopic eczema) is a skin disease that that can affect a person for a long time and causes red or flaky skin that can be itchy and uncomfortable. Healthcare providers can prescribe medicated creams and ointments to reduce the visible signs and symptoms of AD, but these treatments are not always enough to keep it under control. A new medicine called abrocitinib is taken every day as a tablet. Abrocitinib works by slowing a part of the body's defense mechanism, called immune response, that is not functioning properly in AD. The clinical study described in this plain language summary, called JADE DARE, investigated how well and how safely 26 weeks of treatment with abrocitinib worked in adults with AD compared to an injected medicine, called dupilumab, that is also approved for AD. What were the results? The study showed that abrocitinib was more effective than dupilumab in providing itch relief after 2 weeks. In addition, people who were taking abrocitinib for 4 and 16 weeks experienced greater improvement in the visible skin signs of AD than people who were taking dupilumab. The number of people who had health complaints while taking abrocitinib was similar to the number of people who had health complaints while taking dupilumab. Most of these complaints were minor. What do the results mean? Abrocitinib was more effective than dupilumab in quickly improving the signs and symptoms of moderate or severe AD in people who did not show improvement with prescribed medications like creams or ointments. Clinical Trial Registration: NCT04345367 ( ClinicalTrials.gov )

Background Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. Objectives To characterize the plasma inflammatory signature of CHE. Methods Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. Results Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Conclusions Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Background Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. Objectives To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. Methods Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. Results Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87–100%; NPV 68–100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92–100%; NPV 80–100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. Conclusions Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.

BACKGROUND Hand eczema is a common inflammatory skin disorder. Health care providers need continuously updated information about the management of hand eczema to ensure best treatment for their patients. OBJECTIVES To update the European Society of Contact Dermatitis guideline on the diagnosis, prevention, and treatment on of hand eczema. METHOD The Guideline Development Group (GDG) was established on behalf of the ESCD. A call for interest was launched via the ESCD website and via the ESCD members' mailing list. Appraisal of the evidence for therapeutic and preventive interventions was applied and a structured method of developing consensus was used and moderated by an external methodologist. The final guideline was approved by the ESCD executive committee and was in external review on the ESCD webpage for 1 month. RESULTS Consensus was achieved for several statements and management strategies. CONCLUSION The updated guideline should improve management of hand eczema.

Introduction: The comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis (AD) has not been systematically assessed using recent phase 3 data. This network meta-analysis assesses the comparative efficacy of targeted systemic therapies without the addition of topical corticosteroids (TCS) and/or topical calcineurin inhibitors (TCI) in adults with moderate to severe AD. Methods: The systematic literature review searched through 17 May 2021 for phase 3/4 trials with upadacitinib, interleukin-4 (IL-4), interleukin-13 (IL-13), or JAK inhibitors compared with placebo or active intervention for adults and adolescents with moderate to severe AD with inadequate response to TCS/TCI or for whom TCS/TCI was medically inadvisable, without restrictions on year or region. Researchers assessed data using PRISMA guidelines. The proportion of patients achieving trial co-primary endpoints [Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear) and reduction of ≥ 2 points from baseline; proportion of patients achieving Eczema Area and Severity Index (EASI) improvement ≥ 75% from baseline (EASI-75)]; EASI improvement ≥ 90% from baseline (EASI-90); and ≥ 4-point improvement on Pruritus Numerical Rating Scale from baseline (ΔNRS ≥ 4) were evaluated using Bayesian network meta-analysis. Results: Of 3415 initially identified records, network meta-analysis (NMA) ultimately included 6 records representing 9 unique studies. Two upadacitinib trials were also included. Eleven clinical trials including 6254 patients were analyzed. Upadacitinib 30 mg daily was the most efficacious therapy across all endpoints at the primary endpoint (week 12 or 16) and at earlier timepoints, followed by upadacitinib 15 mg daily and abrocitinib 200 mg daily. Discussion: Many factors need to be considered for treatment selection for AD. These findings can help healthcare providers when personalizing a patient’s treatment. Conclusion: Upadacitinib 30 mg daily, upadacitinib 15 mg daily, and abrocitinib 200 mg daily may be the most efficacious targeted systemic therapies over 12–16 weeks of therapy in AD.

Background Skin pain (discomfort/soreness) is a common symptom associated with atopic dermatitis (AD). Objective To evaluate rapid changes in skin pain severity with baricitinib, and its impact on patient quality of life (QoL) in adults with moderate-to-severe AD who were inadequate responders to topical therapy. Methods Adult patients with moderate-to-severe AD who were inadequate responders to topical therapies ( N = 440, BREEZE-AD5 [NCT03435081]) were randomized to once-daily placebo, baricitinib 1 mg, or baricitinib 2 mg for 16 weeks. Change in Skin Pain Numeric Rating Scale (NRS) scores were assessed for the randomized population. Skin Pain NRS and Dermatology Life Quality Index (DLQI) scores were assessed for Skin Pain Response groups and patients with Body Surface Area (BSA) 10% to 50%. Results Skin Pain NRS improvement was significant versus placebo by day 1 baricitinib 2 mg (least squares mean [LSM] difference −4.4%, P = .048) and by day 2 for baricitinib 1 mg (−6.7%, P = .011). As measured weekly, improvement was significant starting at Week 1 and remained significant through Week 16 for both doses. At Week 16, 70.9% of Skin Pain NRS responders vs 10.4% of nonresponders had a clinically meaningful improvement in DLQI ( P < .0001). At week 16, LSM DLQI change from baseline was −11.1 for all Skin Pain NRS responders versus −3.5 for nonresponders ( P < .0001). Patients with BSA 10% to 50% showed similar trends. Conclusions Patients with moderate-to-severe AD, treated with baricitinib, reported rapid improvements in skin pain severity by day 1 for baricitinib 2 mg and day 2 for baricitinib 1 mg and remained effective through 16 weeks of treatment, which positively impacted patient QoL.

There has been no extensive synthesis of studies evaluating the cost of chronic hand eczema (CHE). This review evaluated the societal costs, healthcare resource utilisation, missed work time and job loss due to CHE. MEDLINE and 16 other databases and websites were searched in October 2020 for studies meeting prespecified inclusion criteria. Studies conducted in Europe, Australia, New Zealand or the Americas were included. Two reviewers independently assessed titles and abstracts, and full-text papers published in English between 2000 and 2020, for relevance. Data extraction was carried out by one reviewer and checked by a second reviewer. All data were based on costs between 2001 and 2013 but have been inflated to 2020 prices and converted to US dollars and Euros. A total of 30 studies (reported in 33 publications) were included in the synthesis. Mean total societal costs per year per patient ranged from $2549 (€1813) to $10,883 (€7738). Pharmacological therapy was, on average, $28.34 (€20.15) per month in Italy and $36.49 (€25.94) per month for emollients in Switzerland. Yearly treatment costs were $599.05 (€425.92) for drugs, including topical corticosteroids, topical calcineurin inhibitors, other topical treatments and oral treatments, and $178.40 for emollients, in Germany. CHE was associated with hospitalisation costs ranging from $81.86 (€58.20) per patient per month (US) to $105.04 (€74.68) per patient per month (Italy) and $639.59 (€454.75) per year (Germany). Up to 57% of patients took sick leave and up to 25% reported job loss/job change due to CHE. This review confirms the significant cost burden of CHE. Given the paucity of studies estimating the monetary costs of absenteeism, presenteeism and job loss associated with CHE, current mean societal costs are likely underestimated. Uncontrolled disease may also lead to increased costs to patients and society.

IntroductionLesional skin of atopic dermatitis (AD) is often colonised byStaphylococcus aureusand the bacterial abundance increases during a flare. However, the role ofS. aureusand the skin microbiome in the pathogenesis of AD, including its influence on the dysfunctional skin barrier and immune response, remains to be elucidated. In this study, the temporal relationship between alterations in the skin barrier function, inflammation and microbiome is examined in adults with AD.Methods and analysisThis clinical study consists of 81 adult patients with AD, as defined by the Hanifin and Rajka criteria, and 41 age and sex-matched controls. The objectives are to examine alterations in the skin microbiome, skin barrier and immune response during (1) an untreated AD flare, (2) an AD flare treated with topical corticosteroids (TCS), (3) an AD flare treated with systemic dicloxacillin/placebo and TCS or (4) cutaneous exposure to either autologousS. aureus, staphylococcal enterotoxin B or a vehicle. Skin biopsies, tape strips, skin and nasal swabs are collected and analysed using RNA sequencing, multiplex immunoassays, liquid chromatography-mass spectrometry and 16S rDNA. Blood samples are analysed for filaggrin gene mutations and leucocyte gene expression.Ethics and disseminationThe scientific Ethical Committee of the Capital Region in Denmark (phases I and II: H-20011047, phases III and IV: H-21079287), the local data protection agency (phases I and II: P-2020-165, phases III and IV: P-2022-250) and the Danish Medicines Agency (phases III and IV: EudraCT 2021-006883-25, ClinicalTrials.gov:NCT05578482) have approved the studies. Participants will give written informed consent prior to study initiation. The study is conducted in accordance with the Helsinki Declaration. Outcomes will be presented at national and international conferences and in international peer-reviewed publications.Trial registration numberNCT05578482, EudraCT 2021-006883-2.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with itch, eczematous lesions and impaired quality of life (QoL). Although the frequency of skin pain in AD is often underestimated, it is associated with a substantial health burden, similar to itch and is known to contribute to sleep disruption and mood disturbance. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. In phase 3 clinical trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871), abrocitinib demonstrated rapid relief from itch and skin pain, as well as meaningful improvements in QoL compared with placebo. The interrelationships between abrocitinib treatment and improvements in itch, skin pain and QoL have not yet been investigated. This mediation analysis aimed to characterize the effect of abrocitinib treatment via itch and skin pain on dermatology-specific QoL in patients with AD. Data from JADE MONO-1 and JADE MONO-2 were pooled in this analysis. Adult patients with moderate-to-severe AD received abrocitinib (200 or 100 mg) as monotherapy or placebo for 12 weeks. Three separate models were evaluated whereby QoL was assessed using the Dermatology Life Quality Index (DLQI) score, and itch and skin pain were assessed via the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) items #1 (How itchy was your skin over the past 24 h?) and #2 (How painful was your skin over the past 24 h?), respectively. The cross-sectional mediation model (CSMM) was run separately at weeks 2, 4, 8 and 12 using all available data at each timepoint. The longitudinal mediation model (LMM), which does not assume independence among measurements of itch, skin pain and DLQI at each timepoint, estimated relationships using all available data from all weeks simultaneously. Based on the results of the CSMM and LMM, a pseudo-steady-state model, in which the relationship among variables was assumed to be the same across timepoints, was applied. Effects with P < 0.05 were considered statistically significant. In the CSMM, the indirect effect of abrocitinib on DLQI mediated via itch was considered approximately stable (24–30%) for the first 8 weeks before increasing at week 12 (42%), while the indirect effect mediated via skin pain was considered approximately stable from week 2 to week 12 (33–41%). In the LMM, the indirect effect of abrocitinib treatment on DLQI mediated via both itch and skin pain was considered approximately stable from week 2 to week 12 (17–26% and 42–48%, respectively). The cross-sectional and longitudinal models were generally consistent and indicated a pseudo-steady-state period between weeks 2 and 12. Using the pseudo-steady-state model, the direct effect of abrocitinib on DLQI was estimated to be 34.8% (P < 0.0001), and the indirect effects mediated via itch and skin pain were estimated to be 19.5% and 45.8%, respectively (P ≤ 0.0001 for both). Improvements in dermatology-specific QoL with abrocitinib are mostly mediated indirectly via a reduction in skin pain and less so by relief of itch. These findings warrant further research to examine to what extent patients consider itch and skin pain as separate concepts in terms of their impact on dermatology-specific QoL.

Abrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, had a superior efficacy vs. dupilumab in head-to-head randomized trials in moderate-to-severe atopic dermatitis (AD). Data on patients who switched from dupilumab to abrocitinib have been limited. To evaluate abrocitinib response in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab. Dupilumab-treated patients from the JADE DARE trial (NCT04345367), which was designed to compare the efficacy and safety of 26-week abrocitinib (200 mg daily) vs. dupilumab (300 mg bi-weekly) in patients receiving topical medicated therapy, had the option to switch to abrocitinib 200 mg by enrolling to an open-label JADE EXTEND trial (NCT03422822). In this analysis, we evaluated the response to abrocitinib 200 mg at week 12 of JADE EXTEND of responders and nonresponders to dupilumab at week 26 of JADE DARE. Response and nonresponse were defined as patients’ achievement and nonachievement, respectively, of ≥50%, ≥ 75% or ≥90% improvement from the JADE DARE baseline in Eczema Area and Severity Index (EASI-50, EASI-75 or EASI-90), ≥ 4-point improvement from JADE DARE baseline in Peak Pruritus Numerical Rating Scale (PP-NRS4), and PP-NRS score of 0 or 1 (PP-NRS 0/1) at week 26 of JADE DARE. In addition, changes in individual EASI and PP-NRS scores were evaluated in dupilumab-treated patients with significant skin lesions (EASI ≥16) or itch burden (PP-NRS ≥7) at week 26 of JADE DARE. Patients who withdrew from JADE EXTEND were considered nonresponders after withdrawal. Additionally, adverse events (AEs) of dupilumab-treated patients from JADE DARE occurring during JADE EXTEND were assessed. Out of 365 dupilumab-treated patients in JADE DARE, 312 received treatment in JADE EXTEND. After 12 weeks of switching to abrocitinib, EASI-50 response was maintained in 98% of patients (277/282) who had attained EASI-50 after 26 weeks of dupilumab. Those values were 95% (232/245) for EASI-75, 88% (143/162) for EASI-90, 91% (192/210) for PP-NRS4 and 79% (86/109) for PP-NRS 0/1. Conversely, among patients who did not attain EASI-50 after 26 weeks of dupilumab, switching to abrocitinib for 12 weeks resulted in 75% (12/16) of patients attaining this level of response. Those values were 77% (41/53) for EASI-75, 62% (85/136) for EASI-90, 51% (46/90) for PP-NRS4 and 45% (86/192) for PP-NRS 0/1. Among dupilumab-treated patients with EASI ≥16 at week 26 of JADE DARE, 91% (10/11) experienced improvements (i.e. EASI

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itch, skin pain and impaired quality of life. Skin pain is a common and bothersome symptom of AD and increases in prevalence and intensity with worsening disease severity. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. Abrocitinib treatment resulted in improvements in skin clearance as well as rapid itch reduction in patients with moderate-to-severe AD across multiple phase 3 studies. Work productivity loss and activity impairment were assessed in the phase 3 JADE MONO-2 (NCT03575871) trial, with greater improvements being associated with abrocitinib treatment compared with placebo. The mechanism(s) through which abrocitinib reduces work productivity loss and activity impairment are unclear. To describe the interrelationships among abrocitinib treatment, itch, skin pain, and work productivity and activity impairment using a mediation modelling analysis in patients with AD. Data from adult patients treated with abrocitinib monotherapy (200 or 100 mg) or placebo in JADE MONO-2 were included in this analysis. As separate outcomes, work productivity loss and activity impairment (outcome variables) were measured by the Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis version 2.0 (WPAI-AD 2.0). Itch and skin pain (mediator variables) were evaluated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) item #1 (How itchy was your skin over the past 24 h?) and item #2 (How painful was your skin over the past 24 h?), respectively. Mediation modelling was conducted independently for work productivity loss and activity impairment. All available data at week 12 were used in the modelling. Effects with P < 0.05 were considered statistically significant. The direct effects of abrocitinib were estimated to be 7.3% (P = 0.779) and 17.5% (P = 0.258) on work productivity loss and activity impairment, respectively. The indirect effects of abrocitinib treatment on work productivity loss and, separately, on activity impairment mediated via itch were estimated to be 50.6% (P = 0.017) and 20.9% (P = 0.062), respectively, and via skin, pain were estimated to be 42.1% and 61.5%, respectively, (P < 0.05 for both). The indirect effect of abrocitinib treatment on work productivity loss is mediated approximately equally through the reduction in itch severity and skin pain. The effect of abrocitinib treatment on activity impairment is mostly mediated indirectly through the reduction of skin pain, along with a smaller indirect contribution from the reduction in itch. These findings support further research into the extent that patients consider itch and skin pain as separate concepts in terms of their impact on work productivity.

Atopic dermatitis (AD) is a debilitating chronic inflammatory skin disease with fluctuating disease severity that requires long-term control. Patients report that complete or almost complete skin clearance is highly important as a treatment goal. Upadacitinib is a selective oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 vs. JAK2, JAK3, and tyrosine kinase 2. In this post-hoc analysis of the upadacitinib phase 3/3b studies, we analysed the time patients spent in skin clearance response states over 16 weeks with upadacitinib 15 mg (UPA 15) and 30 mg (UPA 30) compared to placebo and dupilumab. Data were from phase 3/3b multicenter, randomized, double-blinded studies comparing the safety and efficacy of upadacitinib to either placebo (Measure Up 1 and Measure Up 2) or dupilumab (Heads Up) in patients with moderate-to-severe AD. In the Measure Up 1 and Measure Up 2 studies, adults and adolescents were randomized to receive UPA 15, UPA 30 or a placebo once daily for 16 weeks. In the Heads Up study, adults were randomized to receive UPA 30 once daily or dupilumab 300 mg every 2 weeks beginning at week 2 following an initial loading dose of 600 mg. The days patients spent in skin clearance response states based on Eczema Area Severity Index (EASI) improvements ≥75%/90%/100% (EASI 75/90/100) from baseline were assessed. Missing data at study visits were imputed using non-responder imputation. Response states between study visits were interpolated using the last observation carried forward. Integrated data from Measure Up 1 and Measure Up 2 included 1683 adults and adolescents randomized to UPA 15 (N = 557), UPA 30 (N = 567), or placebo (N = 559); 44.0% were female, and 48.8% had previously received systemic therapy. In the Heads Up study, 692 adults were randomized to UPA 30 (N = 348) or dupilumab (N = 344); 45.5% were female, and 51.0% had previously received systemic therapy. Patients in Measure Up 1 and 2 taking UPA 15 or UPA 30 cumulatively spent a greater proportion of days in EASI 75 (UPA 15: 54.2%, UPA 30: 64.6%, Placebo: 10.2%), EASI 90 (UPA 15: 32.0%, UPA 30: 44.0%, Placebo: 3.2%), and EASI 100 (UPA 15: 7.5%, UPA 30: 13.5%, Placebo: 0.6%) response states compared to placebo over 16 weeks. In the Heads Up study, patients taking UPA 30 vs. dupilumab cumulatively spent a greater proportion of days in EASI 75 (58.9% vs. 36.9%), EASI 90 (42.1% vs. 19.1%), and EASI 100 (11.8% vs. 3.3%) response states over 16 weeks. Treatment of moderate-to-severe AD with UPA 15 or UPA 30 resulted in a greater proportion of days spent with higher levels of skin clearance (EASI 75/90/100) compared to placebo over 16 weeks, mirroring findings from the Heads Up study comparing UPA 30 to dupilumab. Increases in time spent with high levels of skin clearance with upadacitinib treatment may reflect improved long-term disease control and translate into more time spent experiencing a better quality of life that is less burdened by AD.

Lebrikizumab is an injectable, IgG4 monoclonal antibody that selectively binds to interleukin-13 with high affinity. Injection-site reactions (ISRs) are localized adverse events in the immediate site of administration of a drug and are common with injectable therapies. This analysis reports ISRs in patients from eight lebrikizumab (LEB) clinical trials in atopic dermatitis. To report ISRs in patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of phase 2 and 3 LEB clinical trials. These data sets include adolescents and adult patients who received at least one dose of LEB from a total of eight atopic dermatitis clinical trials, including four 16-week placebo-controlled clinical trials. Eight trials consist of: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. ISRs were defined using the preferred terms from the Medical Dictionary for Regulatory Activities high-level term, injection site reactions, excluding terms related to joints. This analysis includes ISRs frequencies in patients treated with LEB compared to placebo (ALL PC week 0–16), and all patients who received any dose of LEB (ALL LEB), and reports ISRs type, exposure adjusted incidence rates (EAIR) per 100 patient-years, the timing of ISRs occurrence, and ISRs leading to discontinuation. In the ALL PC week 0–16 analysis, 2.6% (n = 20/783, EAIR 9.0) of patients in the LEB group reported ISRs vs. 1.5% (n = 6/404 EAIR 5.4) in the placebo group. Injection site pain (n = 7, 0.9%) and injection site erythema (n = 7, 0.9%) were the most frequent reactions reported in the LEB group. Most ISRs were mild or moderate, with only 1 (0.1%) severe event. In the ALL LEB analysis, 3.1% of patients reported ISRs (n = 53/1720, EAIR 3.3). Injection site pain (n = 16, 0.9%) and injection site erythema (n = 12, 0.7%) were the most frequent reactions. Almost all reports were mild or moderate, with 3 (0.2%) severe. The incidence of ISRs did not increase with a longer duration of LEB exposure. The majority of ISRs were reported between weeks 0 and 16 (n = 38, 2.2%). The frequency of ISRs from week 16 to 32 was 1.0% (n = 15), from week 32 to 48 was 0.4% (n = 4) and from week 48 to 64 was 0.2% (n = 2). Treatment discontinuation due to ISRs occurred in a few patients (n = 5, 0.3%). Overall, a low proportion of patients reported ISRs (

Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults. We report integrated baricitinib safety data in patients with up to 3.9-years exposure. Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg–4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated. 2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported. In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD. NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7)

The European baseline series was last updated in 2019. This article discusses the reasoning behind a further iteration of the series for 2023.

Background: It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk. Objectives: This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life. Methods: This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD. Results: The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection. Conclusions: This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been developed previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development.