Optimizing maintenance therapy in responders to abrocitinib induction: A post hoc analysis of JADE REGIMEN.

BACKGROUND: Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg-induced response in patients with moderate-to-severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg) or placebo. Maintenance with continuous-dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose. OBJECTIVE: This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring. METHODS: Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40-week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring. RESULTS: Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period. CONCLUSIONS: Maintenance of response using reduced-dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment.

Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of ciclosporin A: a placebo-controlled, randomized, phase III clinical trial (ECZTRA 7).

BACKGROUND: Patients with severe atopic dermatitis (AD) not controlled with topical therapy have limited treatment options. Ciclosporin A (CSA) is a commonly used, broad immunosuppressant in AD, but treatment with CSA requires monitoring for potentially serious adverse effects. In a previous phase III trial, tralokinumab plus topical corticosteroids (TCS) as needed provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab plus TCS in adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA. METHODS: In this 26-week, multicentre, parallel, randomized, double-blind, placebo-controlled, phase III trial, European adults with severe AD were randomized 1 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks plus TCS as needed. The primary endpoint was a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: In total, 277 patients were randomized. At week 16, more patients treated with tralokinumab plus TCS vs. placebo plus TCS achieved EASI 75 [64·2% vs. 50·5%; difference 14·1% (95% confidence interval 2·5-25·7); P = 0·018], which increased further up to week 26. Improvements in AD severity were accompanied by early improvements in patient-reported outcomes, including Dermatology Life Quality Index, Patient-Oriented Eczema Measure, pruritus and sleep interference. Tralokinumab plus TCS also showed a higher EASI75 response at week 16 among patients who had previously failed CSA therapy vs. placebo plus TCS (57% vs. 41%). The overall incidence of adverse events was similar between treatment arms. CONCLUSIONS: Tralokinumab 300 mg plus TCS as needed was effective and well tolerated in patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.

Pioneering global best practices in atopic dermatitis: results from the atopic dermatitis quality of care initiative.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by unrelenting pruritus and recurrent eczematous lesions. It affects up to 15% of children and adolescents and up to 5% of adults, and confers a high and multifactorial burden to patients, families and society. With increasing awareness of this substantial burden, AD has become a priority for healthcare systems. AIM: The Atopic Dermatitis Quality of Care (ADQoC) initiative set out to describe good practices for addressing the challenges that impede the management of AD. METHODS: The initiative carried out a literature review and surveyed 32 expert care centres, catalogued findings, and analysed and elucidated global challenges to AD care along with good practice implementations that can address them. RESULTS: The four challenges to quality care for AD are: (i) misconceptions about AD; (ii) delayed referral and access to AD specialists; (iii) poor patient access to AD treatments and poor adherence to medications; and (iv) managing the complexity of AD and its comorbidities. The initiative highlighted 5 of 10 good practice implementations as high priority for any AD care centre to focus on: (i) clinical assessment and diagnosis; (ii) a structured multidisciplinary care team; (iii) monitoring and evaluating care quality; (iv) patient education and communication; and (v) collaboration and exchange with patient groups. CONCLUSION: These implementations can provide benefits for patients, healthcare providers and the healthcare system. They directly contribute to the efficacy of treatment, improved healthcare provider efficiency, improved education for patients and healthcare providers, and improved costs to healthcare systems. The initiative was launched on https://atopicdermatitiscare.kpmg.co.uk/ to provide an easy-to-use educational platform.

Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts.

BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated. AIM: To identify the core elements of high-quality AD and PSO biomarkers to prepare recommendations for current biomarker research. METHOD: A cross-sectional two-round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU-funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open-ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, 'agreement' was assumed when the responses of ≥70% of the participants were ≥5 points on a 7-point Likert scale for each statement. Priority classification was based on mean scores (<20th percentile = low, 20th to 60th percentile = medium, >60th percentile = high). RESULTS: Twenty-one and twenty-six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares. CONCLUSION: The core requirements that experts agreed on being essential for high-quality AD and PSO biomarkers require rapid validation. Biomarkers can therefore be assessed based on these prioritized requirements.

Atopic dermatitis: disease characteristics and comorbidities in smoking and non-smoking patients from the TREATgermany registry.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. OBJECTIVES: In this study, AD characteristics and its atopic comorbidities are compared in smoking and non-smoking AD patients. METHODS: TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included in TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analysed comparing AD disease characteristics and comorbidities in smokers vs. non-smokers. RESULTS: Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n = 352; 38.8%) and non-smokers, however, lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to non-smoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than non-smokers. Total IgE levels were more elevated in smokers and they displayed a younger age at the initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to non-smokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. CONCLUSIONS: German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial.

BACKGROUND: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy. METHODS: This was a double-blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. RESULTS: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9-21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8-30·6); P < 0·001]. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% of those treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5% and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups. CONCLUSIONS: Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

[Quality of care for patients with atopic dermatitis in Germany-no improvements in indicators after ten years]. / Qualität der dermatologischen Versorgung von Neurodermitis in Deutschland ­ keine Verbesserung der Indikatoren nach 10 Jahren.

BACKGROUND: With AtopicHealth1, the first national care study on atopic dermatitis (AD) was conducted in 2010. At that time, about one third of the patients undergoing treatment by dermatologists showed severe limitations in quality of life, which indicated an insufficient quality of care. The aim of the present study was to characterise the current care of patients with AD undergoing dermatological treatment in comparison between different severity grades, as well as in comparison to 2010 and to psoriasis. METHODS: The Germany-wide multicentre cross-sectional study "AtopicHealth2" recorded clinical data, quality of life (DLQI), therapies, preventive behaviour and patient-defined treatment benefit (PBI). Patients with an indication for systemic therapy were considered moderately to severely affected for subgroup analyses, the others mildly affected. RESULTS: Between 2017 and 2019, 1291 patients (median age 41 years, 56.5% female) were enrolled by 111 centres. Compared with 2010, there were no improvements in quality of life (DLQI 8.5 in both studies), severity (SCORAD 45.4 vs. 42.3 in 2010) or treatment benefit (PBI 2.2 vs. 2.4 in 2010). Moderately to severely affected patients were more likely to show impaired quality of life (45.4% vs. 23.6%) and less likely to have relevant treatment benefits (PBI < 1: 21.3% vs. 13.2%) than mildly affected patients. In contrast to psoriasis, patients with AD revealed higher quality of life limitations (DLQI 8.5 vs. 6.1) and lower treatment benefit (PBI 2.2 vs. 2.8). DISCUSSION: Compared to 2010, there is no improvement in the quality of care for AD in Germany. Compared to psoriasis, patients with AD show higher burden and lower treatment benefit, which underlines the need for therapeutic innovations.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children.

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Baseline characteristics, disease severity and treatment history of patients with atopic dermatitis included in the German AD Registry TREATgermany.

BACKGROUND: The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the 'real-life' situation of health care for patients with AD. OBJECTIVES: Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. METHODS: Patients (≥18 years) with moderate-to-severe AD [objective (o)SCORAD > 20], or with current or previous anti-inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0-72), the oSCORAD (0-83) and the Investigator Global Assessment (IGA; 6-point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six-step Likert scale]. Disease symptoms were assessed by the patient-oriented eczema measure (POEM, 0-28) and numeric rating scales (NRS, 0-10). Health-related quality of life was measured using the dermatological life quality index (DLQI, 0-30). RESULTS: A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either 'current' (12.1%) or 'prescribed' (31.4%) at baseline. CONCLUSIONS: These 'real-life' data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate-to-severe AD.

Atopic dermatitis: the skin barrier and beyond.

BACKGROUND: Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. METHODS: This is a narrative review based on a systematic literature search. CONCLUSIONS: Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high-risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma.

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).

TREatment of ATopic eczema (TREAT) Registry Taskforce: an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema photo- and systemic therapy registries.

BACKGROUND: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off-label use. Patient registries provide valuable evidence for the effects of treatments under real-world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. OBJECTIVES: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. METHODS: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. RESULTS: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face-to-face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow-up items). CONCLUSIONS: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost-effectiveness of photo- and systemic immunomodulatory therapies.

[Decreased professional performance and quality of life in patients with moderate-to-severe atopic eczema : Results from the German atopic eczema registry TREATgermany]. / Verminderte berufliche Leistungsfähigkeit und Lebensqualität bei Patienten mit moderater bis schwerer Neurodermitis : Ergebnisse aus dem Deutschen Neurodermitisregister TREATgermany.

BACKGROUND: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2 years. This paper analyses the association between dermatological quality of life and work limitations. MATERIALS AND METHODS: Treatment modalities and a broad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43 ± 15 years, 38.6% female) were enrolled at 19 recruitment centers; 69% of the patients were employed. RESULTS: Employed persons had DLQI and WLQ scores of 10.6 ± 6.9 points and 17.7 ± 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (p < 0.000). Bootstrapped regression models showed that the limitations in coping with work requirements increase by 1.7% as DLQI increases by one point. Lower quality of life due to AD is most strongly associated with limitations in the area of physical and performance requirements in general. Presenteeism increases by 0.5% as DLQI increases by one point. CONCLUSION: Moderate-to-severe AD has substantial adverse economic impact with mean productivity loss of patients of almost 10%. Future analyses from TREATgermany will address the impact of innovative treatment modalities on quality of life and work productivity of patients with moderate-to-severe AD.

A 5-year randomized trial on the safety and efficacy of pimecrolimus in atopic dermatitis: a critical appraisal.

AIM: The PETITE study (Sigurgeirsson et al.) aimed to compare safety and efficacy of pimecrolimus 1% cream (PIM) and low-to-medium-potency topical corticosteroids (TCS) in children with mild-to-moderate atopic dermatitis (AD). SETTING AND DESIGN: Participants of this 5-year drug-company sponsored multicentre, open-label, parallel-group trial were recruited between April 2004 and October 2005. No details are reported regarding the study sites. STUDY EXPOSURE: Infants aged ≥ 3 to < 12 months with mild-to-moderate AD were randomly assigned in a 1 : 1 ratio to receive either PIM or a low- or medium-potency TCS cream/ointment for 5 years. No information on specific TCS products used was provided. The topical treatment was applied twice daily 'until complete AD clearance or for as long as allowed by the label of the specific TCS', and was reinitiated at the occurrence of first signs and symptoms of AD flares. In the PIM group, exacerbations not controlled by PIM were treated with short-term TCSs. OUTCOMES: Adverse events (AEs) and serious AEs (SAEs) were recorded 'during clinic visits'. In a proportion of the patients, various immunological assessments including antibody titres to common vaccine antigens, immunoglobulin levels, B and T lymphocyte cell counts, and T-cell proliferation tests were performed. The children's growth was assessed by measuring height and weight. AD severity was measured using the Investigator Global Assessment (IGA) score and the percentage of the total body surface area affected. No specific information was provided on the number and scheduling of study visits. Primary outcomes were the incidence of AEs 'of primary clinical interest' and those with a crude incidence of ≥ 5% in either treatment group. Secondary outcome was 'long-term efficacy' defined as IGA ≤ 1 at week 3 and year 5. RESULTS: Patients in the PIM group experienced significantly more AEs [bronchitis (P = 0·02), infected eczema (P ≤ 0·001), impetigo (P = 0·045), nasopharyngitis (P = 0·04)]. No significant differences were seen for the other AEs. The overall incidence of SAEs was slightly higher for PIM (20·5% vs. 17·3%; P = 0·046). The proportion of participants with IGA ≤ 1 at year 5 was 88·7% for PIM and 92·3% for TCS, a success rate difference of 3·6% (95% confidence interval 0·8-6·4) favouring TCS. CONCLUSIONS: Sigurgeirsson et al. conclude that the long-term management of mild-to-moderate AD in children with both TCS and PIM is safe, and that PIM has similar efficacy to TCS. Further, they conclude that their data support the use of PIM as a first-line treatment of mild-to-moderate AD in children.