Transcriptomics- and Genomics-Guided Drug Repurposing for the Treatment of Vesicular Hand Eczema.

Vesicular hand eczema (VHE), a clinical subtype of hand eczema (HE), showed limited responsiveness to alitretinoin, the only approved systemic treatment for severe chronic HE. This emphasizes the need for alternative treatment approaches. Therefore, our study aimed to identify drug repurposing opportunities for VHE using transcriptomics and genomics data. We constructed a gene network by combining 52 differentially expressed genes (DEGs) from a VHE transcriptomics study with 3 quantitative trait locus (QTL) genes associated with HE. Through network analysis, clustering, and functional enrichment analyses, we investigated the underlying biological mechanisms of this network. Next, we leveraged drug-gene interactions and retrieved pharmaco-transcriptomics data from the DrugBank database to identify drug repurposing opportunities for (V)HE. We developed a drug ranking system, primarily based on efficacy, safety, and practical and pricing factors, to select the most promising drug repurposing candidates. Our results revealed that the (V)HE network comprised 78 genes that yielded several biological pathways underlying the disease. The drug-gene interaction search together with pharmaco-transcriptomics lookups revealed 123 unique drug repurposing opportunities. Based on our drug ranking system, our study identified the most promising drug repurposing opportunities (e.g., vitamin D analogues, retinoids, and immunomodulating drugs) that might be effective in treating (V)HE.

Development and Psychometric Validation of a Patient-Reported Outcome Measure to Assess the Signs and Symptoms of Chronic Hand Eczema: The Hand Eczema Symptom Diary (HESD).

INTRODUCTION: Chronic Hand Eczema (CHE) is an inflammatory skin disease of the hands. The Hand Eczema Symptom Diary (HESD) is a new patient-reported outcome measure of worst severity of core CHE signs/symptoms. This study aimed to evaluate content and psychometric validity of the HESD. METHODS: The HESD was developed based on the literature and concept elicitation interviews. Qualitative cognitive debriefing interviews were conducted with CHE patients to assess relevance and understanding of items, response options and recall period. Psychometric properties of the HESD (item performance, dimensionality, reliability, validity, responsiveness and estimation of meaningful change thresholds) were then assessed, first using data from a phase 2b trial (NCT03683719), and confirmed using data from the first 280 participants completing the 16-week treatment phase of a phase 3 trial (NCT04871711). RESULTS: Cognitive debriefing supported item refinement and removal of items and confirmed all items were well understood and relevant to patients. Item properties and dimensionality analyses in the phase 2b data supported removal of additional items, resulting in the 6-item HESD included in the phase 3 trial. Unidimensionality was supported by inter-item correlations (all > 0.70) and Rasch analysis. Internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (Intraclass Correlation Coefficient > 0.89) results were very strong. Construct validity was supported by moderate correlations with concurrent measures (0.53-0.64) and significant differences between severity groups (p < 0.001). Large effect sizes for mean change scores in participants that improved and significant differences between change groups indicated the ability to detect change. Anchor-based analyses supported within-individual responder definitions of ≥ 4-points for improvements in 7-day average HESD scores. CONCLUSION: The HESD is the first CHE-specific, patient-reported outcome measure of CHE signs/symptoms developed and validated in line with regulatory guidance. This article provides evidence of strong content validity and psychometric validity and shows improvements of ≥ 4 points on 7-day average HESD scores represent clinically meaningful, important changes. TRIAL REGISTRATION: NCT03683719, NCT04871711.

Results of patch testing with five fragrance materials hitherto not tested: A dose-finding study in the clinical population.

BACKGROUND: Quantitative risk assessment (QRA) for skin sensitization is used to derive safe use levels of sensitising fragrance ingredients in products. Post-marketing surveillance of the prevalence of contact allergy to these ingredients provides relevant data to help evaluate the performance of these measures. OBJECTIVES: To determine a suitable patch test concentration for five fragrance materials that had hitherto not been tested on a regular basis. These concentrations are then to be used in a surveillance study with patch testing consecutive patients over an extended monitoring period. MATERIALS AND METHODS: Furaneol, CAS.3658-77-3; trans-2-hexenal, CAS.6728-26-3; 4,8-dimethyl-4,9-decadienal, CAS.71077-31-1; longifolene, CAS.475-20-7; benzaldehyde, CAS.10052-7, were patch tested with other fragrance allergens in four clinics. Patch testing was conducted in three rounds, starting with the lowest concentrations of the five ingredients. The doses were increased in the subsequent rounds if no late-appearing positive reactions and virtually no irritant reactions were reported. RESULTS: Overall, 373 patients were tested. No positive allergic reaction was reported to the five ingredients. Patch test results of other fragrance allergens are reported. CONCLUSIONS: The highest test concentrations are each considered safe for patch testing consecutive patients. Further surveillance based on these preparations will evaluate the hypothesis that QRA-driven consumer product levels of these fragrances can prevent sensitization.

Real-world Experience of Abrocitinib Treatment in Patients with Atopic Dermatitis and Hand Eczema: Up to 28-week Results from the BioDay Registry.

Limited daily practice data on the effect of abrocitinib in patients with atopic dermatitis are available. The aim of this multicentre prospective study is to evaluate the effectiveness and safety of abrocitinib in patients with atopic dermatitis treated in daily practice. In a subgroup, the effectiveness of abrocitinib on hand eczema was evaluated. A total of 103 patients from the BioDay registry were included in the study: week 4 (n = 95), week 16 (n = 61) and week 28 (n = 39). At week 28, the Eczema Area and Severity Index (EASI)-50/75/90 was achieved by 81.8%, 57.6%, and 18.2%, respectively, and the weekly average pruritus numerical rating scale ≤ 4 by 62.9%. The effectiveness of abrocitinib was not significantly different between dupilumab non-responders and dupilumab-naïve patients/responders, and between upadacitinib non-responders and upadacitinib-naïve patients/responders. Mean ± standard deviation Hand Eczema Severity Index decreased from 27.4 ± 27.7 at baseline to 7.7 ± 12.1 at week 28 (n = 31). Thirty-two patients (31.1%) discontinued treatment due to ineffectiveness (n = 17), adverse events (n = 9) or both (n = 3). The most frequently reported adverse event was nausea (n = 28). In conclusion, abrocitinib is an effective treatment for atopic dermatitis and can be effective for patients with previous inadequate response to dupilumab or upadacitinib. Furthermore, hand eczema can improve in patients treated with abrocitinib for atopic dermatitis.

Hand eczema-related presenteeism and sickness absence: A cross-sectional population-based study.

BACKGROUND: To date, hand eczema (HE)-related presenteeism has never been assessed within the general population, and general population-based studies on HE-related sickness absence are limited. OBJECTIVES: To assess the prevalence of HE-related presenteeism and sickness absence, and factors associated with HE-related presenteeism, within the Dutch general population. METHODS: Within the Lifelines Cohort Study, participants with HE in the last year (aged 18-65 in 2020), were identified by a questionnaire including questions regarding HE-related presenteeism and sickness absence. Socio-demographic factors were collected from 2006 to 2020. RESULTS: Out of the 3.703 included participants with HE, 2.7% (n = 100) reported HE-related presenteeism, with 19.8% (n = 57) among those with severe-to-very-severe HE. HE-related sickness absence was reported by 0.5% (n = 20) and 5.9% (n = 17), respectively. Logistic regression analyses, adjusted for age and sex, showed negative associations between HE-related presenteeism and higher educational attainment, higher income (>€2500) and higher occupational skill level, and positive associations for high-risk occupations, chronic HE, moderate and severe-to-very-severe HE (compared to almost clear), atopic dermatitis and occupational wet exposure. CONCLUSIONS: A high prevalence of HE-related presenteeism was found among participants with severe-to-very-severe HE. Future studies should focus on longitudinal associations with the clinical course of HE, as HE-related presenteeism might aggravate symptoms of HE.

The construct validity, responsiveness, reliability and interpretability of the Recap of atopic eczema questionnaire (RECAP) in children.

BACKGROUND: The Recap of atopic eczema questionnaire (RECAP) was developed to measure eczema control in patients with atopic dermatitis (AD). The measurement properties of RECAP have not yet been validated in caregivers of children with AD. OBJECTIVES: To assess the construct validity, responsiveness, reliability and interpretability of the Dutch proxy version of RECAP. METHODS: A prospective validation study was conducted in children (aged < 12 years) with AD and their caregivers (in a Dutch tertiary hospital). At three timepoints (T0 = baseline; T1 = after 1-7 days; T2 = after 4-8 weeks) RECAP and multiple reference instruments were completed by caregivers of child patients. Single- and change-score validity (responsiveness) were tested with a priori hypotheses on correlations with reference instruments. Intraclass correlation coefficients (ICCagreement) and standard error of agreement (SEMagreement) were reported. Bands for perceived eczema control were proposed. The smallest detectable change (SDC) and minimally important change (MIC) were determined. Two anchor-based methods based on receiver operating characteristic curve (ROC) and predictive modelling were used to determine the MIC. RESULTS: A total of 231 children with AD and their caregivers participated. Of our a priori hypotheses for single-score and change-score validity, 77% and 80% were confirmed, respectively. A stronger correlation than hypothesized was found for all rejected hypotheses.Excellent reliability was found (ICCagreement = 0.94, 95% confidence interval 0.90-0.96). The SEMagreement was 1.9 points. The final banding was 0-1 (completely controlled), 2-7 (mostly controlled), 8-12 (moderately controlled), 13-18 (a little controlled) and 19-28 (not at all controlled). A cutoff point of ≥ 8 was selected to identify children whose AD is not under control. The SDC was 5.3 and the MIC values were 1.5 and 3.6 for the ROC and predictive modelling approaches, respectively. No floor or ceiling effects were observed. CONCLUSIONS: The proxy version of RECAP is a valid, reliable and responsive measurement instrument for measuring eczema control in children with AD. An improvement of ≥ 6 points can be regarded as a real and important change in children with AD.

Atopic dermatitis (AD) is a skin disease that affects children and adults. People with AD (eczema) and other stakeholders have identified perceived 'eczema control' as an important outcome to investigate in research. For this purpose, the Recap of atopic eczema (RECAP) questionnaire was developed, consisting of seven items to measure eczema control in people with AD. However, when developing questionnaires, they must be examined to ensure they are relevant, reliable and sensitive enough to detect meaningful change before and after any new treatment. Prior studies have demonstrated that the RECAP is suitable for adults with AD, but studies investigating whether the RECAP is suitable for children are lacking. A study of 231 children (under 12 years old) with AD and their caregivers was conducted in the Netherlands. Caregivers completed the RECAP questionnaire at three time points: at the start of the study, after 1­7 days and after 4­8 weeks. The researchers assessed AD severity and eczema control using other measures for comparison. RECAP scores from children whose caregivers reported unchanged eczema control were used to assess how reproducible this questionnaire was. RECAP scores of caregivers who reported change in eczema control were used to examine sensitivity to change. Statistical tests were used to analyse findings. The researchers found that RECAP accurately measures changes in eczema control over time and was sensitive enough to detect small changes in eczema control. Overall, the authors concluded that the RECAP questionnaire is valid, reproducible and responsive. Furthermore, they consider an improvement of at least 6 points to represent a genuine improvement in Dutch children.

Dupilumab treatment improves signs, symptoms, quality of life, and work productivity in patients with atopic hand and foot dermatitis: Results from a phase 3, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited. OBJECTIVES: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet. METHODS: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep. RESULTS: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile. LIMITATIONS: Short-term, 16-week treatment period. CONCLUSION: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition.

Effectiveness of antibacterial therapeutic clothing vs. nonantibacterial therapeutic clothing in patients with moderate-to-severe atopic dermatitis: a randomized controlled observer-blind pragmatic trial (ABC trial).

BACKGROUND: Increased Staphylococcus aureus (SA) colonization is considered an important factor in the pathogenesis of atopic dermatitis (AD). Antibacterial therapeutic clothing aims to reduce SA colonization and AD inflammation; however, its role in the management of AD remains poorly understood. OBJECTIVES: To investigate the effectiveness of antibacterial therapeutic clothing + standard topical treatment in patients with moderate-to-severe AD vs. standard therapeutic clothing + standard topical treatment; and, if effectiveness was demonstrated, to demonstrate its cost-effectiveness. METHODS: A pragmatic double-blinded multicentre randomized controlled trial (NCT04297215) was conducted in patients of all ages with moderate-to-severe AD. Patients were centrally randomized 1 : 1 : 1 to receive standard therapeutic clothing or antibacterial clothing based on chitosan or silver. The primary outcome was the between-group difference in Eczema Area and Severity Index (EASI) measured over 52 weeks. Secondary outcomes included patient-reported outcomes (PROs), topical corticosteroid (TCS) use, SA colonization, safety and cost-effectiveness. Outcomes were assessed by means of (generalized) linear mixed-model analyses. RESULTS: Between 16 March 2020 and 20 December 2021, 171 patients were enrolled. In total, 159 patients were included (54 in the standard therapeutic clothing group, 50 in the chitosan group and 55 in the silver group). Adherence was high [median 7 nights a week wear (interquartile range 3-7)]. Median EASI scores at baseline and at 4, 12, 26 and 52 weeks were 11.8, 4.3, 4.6, 4.2 and 3.6, respectively, in the standard therapeutic clothing group vs. 11.3, 5.0, 3.0, 3.0 and 4.4, respectively, in the chitosan group, and 11.6, 5.0, 5.4, 4.6 and 5.8, respectively, in the silver group. No differences in EASI over 52 weeks between the standard therapeutic clothing group, the chitosan group [-0.1, 95% confidence interval (CI) -0.3 to 0.2; P = 0.53] or the silver group (-0.1, 95% CI -0.3 to 0.2; P = 0.58) were found. However, a small significant group × time interaction effect between the standard and silver groups was found (P = 0.03), in which the silver group performed worse after 26 weeks. No differences between groups were found in PROs, TCS use, SA skin colonization and healthcare utilization. No severe adverse events or silver absorption were observed. CONCLUSIONS: The results of this study suggest no additional benefits of antibacterial agents in therapeutic clothing in patients with moderate-to-severe AD.

Therapeutic clothing use in atopic dermatitis in the Netherlands: A population based cohort study.

National prescription data for therapeutic clothing in atopic dermatitis was analysed to investigate the role of therapeutic clothing in atopic dermatitis. Therapeutic clothing is most frequently prescribed by dermatologists in a hospital setting. Most patients only receive one prescription of therapeutic clothing, suggesting a limited role for therapeutic clothing in the long-term management of atopic dermatitis.

Remote severity assessment in atopic dermatitis: Validity and reliability of the remote Eczema Area and Severity Index and Self-Administered Eczema Area and Severity Index.

Background: Reliable assessment of atopic dermatitis (AD) severity is necessary for clinical practice and research. Valid and reliable remote assessment is essential to facilitate remote care and research. Objectives: Assess the validity and reliability of the Eczema Area and Severity Index (EASI) based on images and patient-assessed severity based on the Self-Administered EASI (SA-EASI). Methods: Whole-body clinical images were taken during consultation from children with AD. After consultations, caregivers completed the SA-EASI and provided images from home. Four raters assessed all images twice using EASI. Results: A total of 1534 clinical images and 425 patient-provided images were collected from 87 and 32 children. Excellent (0.90) validity, good inter (0.77) and intrarater reliability (0.91), and standard error of measurement (4.31) was found for the EASI based on clinical images. Feasibility of patient-provided images showed limitations with missing images (43.8%) and quality issues (23.1%). However, good validity (0.86), inter (0.74) and intrarater reliability (0.94) were found when assessment was possible. Moderate correlation (0.60) between SA-EASI and EASI was found. Limitations: Low portion patient-provided images. Conclusion: AD severity assessment based on images strongly correlates with in-person AD assessment. Good measurement properties confirm the potential of remote assessment. Moderate correlation between SA-EASI and in-person EASI suggest limited value of self-assessment.

Perceived adherence and associated barriers to the national atopic dermatitis guideline: A survey among general practitioners.

BACKGROUND: General practitioners (GPs) have an important role in managing patients with atopic dermatitis (AD). Although pivotal, adherence to dermatological guidelines in general practice has not been assessed. OBJECTIVES: To assess GPs' perceived adherence and barriers to the Dutch AD guideline. METHODS: A survey was conducted among 391 GPs in the Netherlands between December 2021 and May 2022. GPs rated their perceived adherence and perceived barriers concerning five key recommendations of the AD guideline, following an existing framework. The correlation between perceived adherence and barriers was investigated using Spearman's rank correlation. RESULTS: A total of 213 GPs (54%) participated. Perceived adherence rates varied across recommendations (43.7% to 98.1%). Lowest adherence was reported for recommendations concerning topical corticosteroids (TCS). Across all recommendations, patient factors (65.6%; SD 11.6) and lack of applicability to specific patient groups (29.5%; SD 10.5) were reported most frequently as barriers. The overall correlation between adherence and barriers was strongest for knowledge (ρ .55; SD .10) and attitude-related factors (range: ρ .40--.62). CONCLUSION: GPs' perceived adherence and barriers vary substantially across recommendations of the AD guideline. In particular, GPs reported lower adherence to recommendations concerning TCS. Next to patient-related factors, strong correlations between adherence perceived by GPs and knowledge and attitude-related barriers suggest the importance of addressing these factors as well to improve adherence.

Beyond Anxiety and Depression: Loneliness and Psychiatric Disorders in Adults with Atopic Dermatitis.

There is a lack of knowledge concerning loneliness and psychiatric disorders other than anxiety and depression in patients with atopic dermatitis. This cross-sectional study was conducted within the Lifelines Cohort Study, in the Netherlands, by sending an atopic dermatitis questionnaire to adult participants (n = 135,950) in 2020. Psychiatric disorders were measured with a self-reported question and validated instrument (Mini International Neuropsychiatric Interview; M.I.N.I.), and loneliness was assessed with the validated 6-item De Jong Gierveld Loneliness Scale. In total, 56,896 subjects (mean age 55.8 years, 39.7% males) were included. Atopic dermatitis showed positive associations with self-reported chronic fatigue syndrome, burnout, depression, social phobia, panic disorder, attention deficit hyperactivity disorder, and eating disorder in the participants' lifetimes. Based on the M.I.N.I., atopic dermatitis was positively associated with panic disorder and at least 1 anxiety disorder. In addition, subjects with atopic dermatitis were more likely to experience loneliness compared with those without atopic dermatitis. These associations were observed only in the moderate-to-severe, but not mild, atopic dermatitis group. This study raises awareness that a significant proportion of adults with atopic dermatitis feel lonely and are affected by several psychiatric disorders, especially those severely affected by atopic dermatitis. Further studies are required to evaluate if interdisciplinary care, such as the collaboration between dermatologists and psychiatrists, could optimize medical care for this vulnerable patient group.

Validity, reliability, responsiveness and interpretability of the Recap of atopic eczema (RECAP) questionnaire.

BACKGROUND: Limited research has been conducted on the measurement properties of the Recap of atopic eczema (RECAP) questionnaire, particularly in relation to interpretability. OBJECTIVES: To investigate the validity, reliability, responsiveness and interpretability of the Dutch RECAP in adults with atopic dermatitis (AD). METHODS: We conducted a prospective study in a Dutch tertiary hospital, recruiting adults with AD between June 2021 and December 2022. Patients completed the RECAP questionnaire, reference instruments and anchor questions at the following three timepoints: baseline, after 1-3 days and after 4-12 weeks. Hypotheses testing was used to investigate single-score validity and change-score validity (responsiveness). To assess reliability, both standard error of measurement (SEMagreement) and intraclass correlation coefficient (ICCagreement) were reported. To assess the interpretability of single scores, bands for eczema control were proposed. To investigate the interpretability of change scores, both smallest detectable change (SDC) and minimally important change (MIC) scores were determined. To estimate the MIC scores, four different anchor-based methods were employed: the mean change method, 95% limit cut-off point, receiver operating characteristic curve and predictive modelling. RESULTS: In total, 200 participants were included (57.5% male sex, mean age 38.5 years). Of the a priori hypotheses, 82% (single-score validity) and 59% (responsiveness) were confirmed. Known-group analyses showed differences in the RECAP scores between patient groups based on disease severity and impairment of the quality of life. The SEMagreement was 1.17 points and the ICCagreement was 0.988. The final banding was as follows: 0-1 (completely controlled); 2-5 (mostly controlled); 6-11 (moderately controlled); 12-19 (a little controlled); 20-28 (not at all controlled). Moreover, a single cut-off point of ≥ 6 was determined to identify patients whose AD is not under control. The SDC was 3.2 points, and the MIC value from the predictive modelling was 3.9 points. Neither floor nor ceiling effects were observed. CONCLUSIONS: The RECAP has good single-score validity, moderate responsiveness and excellent reliability. This study fills a gap in the interpretability of the RECAP. Our results indicate a threshold of ≥ 6 points to identify patients whose AD is 'not under control', while an improvement of ≥ 4 points represents a clinically important change. Given its endorsement by the Harmonising Outcome Measures for Eczema initiatives, the results of this study support the integration of RECAP into both routine clinical practice and research settings.

Efficacy and safety of dupilumab in patients with severe chronic hand eczema with inadequate response or intolerance to alitretinoin: a randomized, double-blind, placebo-controlled phase IIb proof-of-concept study.

BACKGROUND: Effective treatment options for patients with chronic hand eczema (CHE) are scarce. Dupilumab is licensed for the treatment of moderate-to-severe atopic dermatitis and has shown promising results for the treatment of hand eczema in other studies. OBJECTIVES: To evaluate the efficacy and safety of dupilumab in adult patients with severe CHE (subtypes recurrent vesicular hand eczema or chronic fissured hand eczema) who have an inadequate response/intolerance to alitretinoin, or when alitretinoin is medically inadvisable. METHODS: In this 16-week, randomized, double-blind, placebo-controlled proof-of-concept phase IIb trial, patients with severe CHE were randomized 2 : 1 to dupilumab 300 mg or placebo subcutaneously every 2 weeks. Patients visited the outpatient clinic at the initiation of the study drug, and every 4 weeks until 16 weeks of treatment. The primary endpoint was the proportion of patients achieving at least a 75% improvement on the Hand Eczema Severity Index score (HECSI-75) at week 16. Adverse events were monitored during each visit. The study was registered on ClinicalTrials.gov (identifier NCT04512339). RESULTS: In total, 30 patients were randomized, and 29 patients received the assigned study drug (dupilumab n = 20, placebo n = 9). At week 16, more patients achieved HECSI-75 in the dupilumab group than in the placebo group {95% [95% confidence interval (CI) 73.1-99.7] vs. 33% [95% CI 9.0-69.1]}. Dupilumab also showed greater least square mean percentage change from baseline to week 16 in peak pruritus Numerical Rating Scale compared with placebo [-66.5 ± 10.7 (95% CI -88.6 to -44.5) vs. -25.3 ± 17.0 (95% CI -60.1-9.4)]. Adverse events were similar for the dupilumab and placebo groups and were mostly mild. There were no serious adverse events, nor did any of the adverse events lead to discontinuation of the study drug. CONCLUSIONS: Dupilumab was efficacious and well tolerated. Larger studies of longer duration are needed to provide more evidence on the -efficacy of dupilumab in CHE. Moreover, larger studies could also enable comparisons between clinical subtypes or aetiological -diagnoses.

Efficacy and Safety of Tralokinumab in Adolescents With Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial.

Importance: Safe and effective long-term treatments for adolescents with moderate to severe atopic dermatitis (AD) are limited. Objective: To evaluate the efficacy and safety of interleukin-13-targeted treatment with tralokinumab monotherapy in adolescents with AD. Design, Setting, and Participants: The 52-week, randomized, double-blinded, placebo-controlled, phase 3 ECZTRA 6 trial was conducted from July 17, 2018, through March 16, 2021, at 72 centers across 10 countries in North America, Europe, Asia, and Australia. Enrolled patients were 12 to 17 years old with moderate to severe AD (Investigator's Global Assessment [IGA] score ≥3; Eczema Area and Severity Index [EASI] ≥16). Interventions: Patients were randomized (1:1:1) to tralokinumab (150 or 300 mg) or placebo every 2 weeks for 16 weeks. Patients with an IGA score of 0 (clear) or 1 (almost clear) and/or 75% or higher improvement in EASI (EASI 75) at week 16 without rescue medication received maintenance treatment; other patients switched to open-label tralokinumab, 300 mg, every 2 weeks. Main Outcomes and Measures: Primary end points at week 16 were an IGA score of 0 or 1 and/or achieving EASI 75. Key secondary end points were a reduction of Adolescent Worst Pruritus Numeric Rating Scale of 4 or more, change in SCORing AD, and change in Children's Dermatology Life Quality Index from baseline to week 16. Safety end points were the number of adverse events and serious adverse events. Results: Of 301 patients randomized, 289 comprised the full analysis set (median [IQR] age, 15.0 [13.0-16.0] years; 149 [51.6%] male). More patients receiving tralokinumab, 150 mg, (n = 98), and tralokinumab, 300 mg (n = 97), achieved an IGA score of 0 or 1 without rescue medication at week 16 (21 [21.4%] and 17 [17.5%], respectively) vs placebo (n = 94; 4 [4.3%]) (adjusted difference, 17.5% [95% CI, 8.4%-26.6%]; P < .001 and 13.8% [95% CI, 5.3%-22.3%]; P = .002, respectively). More patients receiving tralokinumab, 150 mg (28 [28.6%]), and tralokinumab, 300 mg, (27 [27.8%]) vs placebo (6 [6.4%]) achieved EASI 75 without rescue at week 16 (adjusted difference, 22.5% [95% CI, 12.4%-32.6%]; P < .001 and 22.0% [95% CI, 12.0%-32.0%]; P < .001, respectively). Proportions of patients with Adolescent Worst Pruritus Numeric Rating Scale reduction of 4 or more from baseline were greater with tralokinumab, 150 mg (23.2%), and tralokinumab, 300 (25.0%), vs placebo (3.3%), and adjusted mean changes were greater in SCORing AD with tralokinumab, 150 mg (-27.5), and tralokinumab, 300 mg (-29.1), vs placebo (-9.5) and in Children's Dermatology Life Quality Index with tralokinumab, 150 mg (-6.1), and tralokinumab, 300 mg (-6.7), vs placebo (-4.1) at week 16. At week 52, tralokinumab efficacy was maintained without rescue in more than 50% of patients meeting primary end point(s) at week 16. In the open-label phase, IGA score of 0 or 1 and EASI 75 were achieved in 33.3% and 57.8%, respectively, at week 52. Tralokinumab was well tolerated, without frequency of conjunctivitis increasing through week 52. Conclusions and Relevance: In this randomized clinical trial, tralokinumab was efficacious and well tolerated, supporting its value for treating adolescents with moderate to severe AD. Trial Registration: ClinicalTrials.gov Identifier: NCT03526861.

Experiences from daily practice of upadacitinib treatment on atopic dermatitis with a focus on hand eczema: Results from the BioDay registry.

BACKGROUND: Real-world data on the effectiveness of upadacitinib on atopic dermatitis (AD), hand eczema (HE) and HE in the context of AD are limited. OBJECTIVES: To evaluate the effectiveness and safety of upadacitinib on AD and on HE in patients with AD. METHODS: This prospective observational cohort study includes clinical outcomes: Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), Hand Eczema Severity Index (HECSI), Photographic guide; and PROMs: average pruritus and pain Numeric Rating Scale (NRS) score of the past week, Patient-Oriented Eczema Measure (POEM), Patient-Oriented Eczema, Dermatology Life Quality Index (DLQI), Atopic Dermatitis Control Tool (ADCT), Patient Global Assessment of Disease (PGAD), Quality Of Life Hand Eczema Questionnaire (QOLHEQ) at baseline, Week 4, and Week 16 of upadacitinib-treated patients. Adverse events were monitored during each visit. RESULTS: Thirty-eight patients were included, of which 32 patients had HE. At Week 16, EASI-75 was achieved by 50.0%. Absolute cutoff score NRS-pruritus ≤4 was reached by 62.5%, POEM ≤7 by 37.5%, DLQI ≤5 by 59.4%, ADCT <7 by 68.8%, and PGAD rating of at least 'good' by 53.1%. HECSI-75 was achieved by 59.3% and (almost) clear on the Photographic guide by 74.1%. The minimally important change in QOLHEQ was achieved by 57.9%. Sub-analysis in patients with concomitant irritant contact dermatitis showed no differences. Safety analysis showed no new findings compared to clinical trials. CONCLUSIONS: Upadacitinib can be an effective treatment for patients with AD and concomitant HE in daily practice. Future studies should focus on the effectiveness of upadacitinib on chronic HE, especially on the different etiological subtypes of HE, including HE in non-atopic individuals.

Limited Health Literacy and Its Associated Health Outcomes Among Adults With at Least 2 Atopic Diseases.

BACKGROUND: Health literacy (HL) is essential for patients with multiple atopic diseases to improve their health, given the complexity of their disease and treatment regimens. OBJECTIVE: To estimate the proportion of adults with multiple atopic diseases (at least 2 of atopic dermatitis, asthma, allergic rhinitis, and food allergy) in the Dutch general population and to evaluate the prevalence of limited HL, and its association with socioeconomic status (SES), lifestyle factors, and health-related quality of life (HR-QoL) in this patient population. METHODS: This cross-sectional study was conducted within the Lifelines Cohort Study via sending an add-on digital questionnaire, including (among others) questions on atopic dermatitis, to all adult participants (n = 135,950) between February and May 2020. Data on asthma, allergic rhinitis, lifestyle factors, HR-QoL, and SES were extracted from baseline assessment between 2006 and 2013. Functional, communicative, and critical HL were measured by validated items from Chew and the Dutch Functional Communicative and Critical Health Literacy questionnaires between 2012 and 2016. Food allergy was measured by the Food Allergy Questionnaire between 2014 and 2016. RESULTS: In total, 11.8% of the overall study population reported ever having multiple atopic diseases; of those, 23.6% reported having limited functional HL, with a higher prevalence among those with a low SES. Limited functional HL showed positive associations with smoking, obesity, chronic stress, a low diet quality, and decreased HR-QoL among subjects with multiple atopic diseases. CONCLUSIONS: We identified an HL deficit, and its association with a low SES and poor health outcomes among patients with multiple atopic diseases. Further research is warranted to utilize a more extensive assessment to measure HL and include more health outcomes, such as treatment adherence and disease control.