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

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

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.

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Systemic anti-inflammatory treatment of atopic dermatitis during conception, pregnancy and breastfeeding: Interdisciplinary expert consensus in Northern Europe.

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.

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

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

Upadacitinib for moderate-to-severe atopic dermatitis: Stratified analysis from three randomized phase 3 trials by key baseline characteristics.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib. OBJECTIVES: Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD. METHODS: Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated. RESULTS: A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin. CONCLUSIONS: Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up).

Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events.

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

Prevalence of and association between atopic dermatitis and food sensitivity, food allergy and challenge-proven food allergy: A systematic review and meta-analysis.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

Association between atopic dermatitis and hypertension: a systematic review and meta-analysis.

BACKGROUND: Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension. OBJECTIVES: To determine whether AD and AD severity are associated with hypertension. METHODS: A systematic review was performed of published studies in Ovid MEDLINE, Embase, Scopus, Web of Science, and GREAT (Global Resource for EczemA Trials) databases. At least two reviewers conducted title/abstract, full-text review and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale. RESULTS: Fifty-one studies met the inclusion criteria and 19 had sufficient data for meta-analysis. AD was associated with higher odds of hypertension compared with healthy controls [increased in nine of 16 studies; pooled prevalence 16·4% vs. 13·8%; random-effects regression, pooled unadjusted odds ratio (OR) 1·16, 95% confidence interval (CI) 1·04-1·30], but lower odds of hypertension compared with psoriasis [decreased in five of eight studies; 15·4% vs. 24·8% (OR 0·53, 95% CI 0·37-0·76)]. In particular, moderate-to-severe AD was associated with hypertension compared with healthy controls [increased in four of six studies; 24·9% vs. 14·7% (OR 2·33, 95% CI 1·10-4·94)]. Hypertension was commonly reported as an adverse event secondary to AD treatments, particularly systemic ciclosporin A. Limitations include lack of longitudinal studies or individual-level data, and potential confounding. CONCLUSIONS: AD, particularly moderate-to-severe disease, was associated with increased hypertension compared with healthy controls, but with lower odds than for psoriasis.

Conjunctivitis in adult patients with moderate-to-severe atopic dermatitis: results from five tralokinumab clinical trials.

BACKGROUND: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin-13, effectively reduces moderate-to-severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. OBJECTIVE: To analyse conjunctivitis data recorded in five randomized, placebo-controlled trials of tralokinumab in adult patients with moderate-to-severe AD. METHODS: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran-Mantel-Haenszel weights were applied to calculate the adjusted incidence of adverse events. RESULTS: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. LIMITATIONS: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. CONCLUSIONS: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient.

Adults with concomitant atopic dermatitis and asthma have more frequent urgent healthcare utilization and less frequent scheduled follow-up visits than adults with atopic dermatitis or asthma only: a nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) and asthma often co-occur in the same patient, and healthcare utilization is related to disease severity of these diseases. OBJECTIVE: The objective of the study was to investigate differences in healthcare utilization in adults with concomitant AD and asthma compared to patients with asthma or AD only. METHODS: All Danish adults with a hospital diagnosis of AD, asthma or concomitant AD, and asthma recorded in national registries were included. Healthcare utilization data were obtained in 3-month intervals from 2 years prior to index date (the date of the first hospital diagnosis) and to 5 years after. RESULTS: A total of 12 409 patients with AD were included (11 590 with AD only and 819 with concomitant AD and asthma), and 65 539 with asthma only. Adults with concomitant AD and asthma had higher risk of hospitalization for AD (OR 1.38, 95% CI (1.15-1.67), P = 0.001) and asthma (OR 1.16, 95% CI (1.00-1.35), P = 0.047) compared to patients with only AD and asthma, respectively. These patients also had fewer visits in outpatient clinics for AD (OR 0.10, 95% CI (0.08-0.12), P < 0.001) and asthma (OR 0.34, 95% CI (0.29-0.39), P < 0.001) compared to patients with only AD or asthma. Outpatient clinic visits for rhinitis were more frequent among patients with concomitant AD and asthma compared to patients with only AD or asthma. CONCLUSION: Adults with concomitant AD and asthma had different patterns of healthcare utilization compared to adults with AD or asthma alone, suggesting that improvements in management and monitoring may reduce unscheduled healthcare visits and lower healthcare costs.

Long-term follow-up of hand eczema in hairdressers: a prospective cohort study of Danish hairdressers graduating from 1985 to 2007.

BACKGROUND: Occupational hand eczema is common among hairdressers and implementing effective preventive measures requires a good understanding of the disease's epidemiology. OBJECTIVE: To investigate the long-term development of hand eczema (HE) in hairdressers. METHODS: A prospective cohort study of all hairdressers graduating from Danish hairdressing vocational schools from 1985 to 2007 was conducted. A self-administered questionnaire was sent in 2009 with follow-up in 2020. Data from the Danish labour market supplementary pension scheme provided information on yearly affiliation with the hairdressing trade. RESULTS: The cumulative lifetime prevalence of HE increased from 42.3% at baseline to 45.2% at follow-up (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0-1.2). The incidence rate decreased from 42.8 cases/1000 person-years (95% CI, 40.8-44.8) at baseline to 3.4 cases/1000 person-years (95% CI, 2.5-4.6) within the follow-up period. HE onset occurred within 8 years of beginning an apprenticeship for >90% of cases and occurred within the apprenticeship period for 68% of cases. The risk factors associated with having had HE at baseline were a previous positive patch test (adjusted OR [aOR], 5.3; 95% CI, 4.2-6.6), a history of atopic dermatitis (aOR, 3.4; 95% CI, 2.9-4.0) and female sex (aOR, 1.8; 95% CI 1.4-2.3). The most important risk factors at follow-up were previous HE (aOR, 10.1; 95% CI, 7.3-13.8) and a positive patch test within the follow-up period (aOR, 4.5; 95% CI, 3.0-6.8). Among the hairdressers who had HE at baseline, 65.5% exhibited remission, whereas 34.6% had persistent and often severe HE at follow-up. Hairdressers with persistent HE were the subgroup of the study population most frequently affected by the risk factors identified for HE. CONCLUSIONS: Primary prevention of HE should focus on hairdressing apprentices and fully trained hairdressers who have recently graduated. Approximately one-third of trained hairdressers develop persistent and often severe HE, emphasizing the need for early intervention.

High threshold efficacy responses in moderate-to-severe atopic dermatitis are associated with additional quality of life benefits: pooled analyses of abrocitinib monotherapy studies in adults and adolescents.

BACKGROUND: Once-daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate-to-severe atopic dermatitis (AD) in randomized controlled studies. OBJECTIVE: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality-of-life (QoL) benefits. METHODS: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO-1; NCT03575871/JADE MONO-2) in adult and adolescent patients (N = 942) with moderate-to-severe AD receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]-75 and ≥4-point improvement in Pruritus Numerical Rating Scale [PP-NRS4]) and higher threshold efficacy end points (EASI-90 to

Factors associated with ocular surface disease and severity in adults with atopic dermatitis: a nationwide survey.

BACKGROUND: Ocular surface diseases (OSDs), including conjunctivitis and blepharitis, are common in atopic dermatitis (AD) patients, but the magnitude and patient characteristics are unclear. OBJECTIVES: To examine the prevalence of OSDs in adults with AD and identify patient characteristics and risk factors. METHODS: We designed a cross-sectional questionnaire-based survey and sent it via a secure public mail to all adult Danes with a hospital diagnosis of AD (ICD-10 code L20.x) registered in the National Patient Register (n = 16 718) between 2000 and 2019 and 7044 (42%) participated. Primary outcomes were OSDs and severity according to Ocular Surface Disease Index (OSDI). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals (CIs) using logistic regression models. RESULTS: Respondents were mostly females and middle-aged (67.4%, mean [SD] age, 39.0 [15.5] years). Based on Patient-Oriented SCORing Atopic Dermatitis 49% had mild AD, 35% moderate, 10% severe and in 6% AD was inactive; 44.3% reported physician-diagnosed asthma bronchiale and 55.8% rhinitis. The lifetime prevalence of OSDs was 66.6% for conjunctivitis, 63.5% for hordeolum, 11.0% for blepharitis, 9.7% for keratitis, 2.0% for pterygium, 1.5% for symblepharon, 1.1% for keratoconus and 12.7% reported current conjunctivitis. Factors associated with lifetime occurrence of conjunctivitis included mild, moderate, and severe AD (aOR = 1.48 [95% CI, 1.02-2.14], aOR = 1.73 [95% CI, 1.19-2.53], aOR = 2.17 [95% CI, 1.42-3.21]), asthma bronchiale and rhinitis (aOR = 1.76 [95% CI, 1.49-2.07]), childhood-onset of AD (aOR = 1.34 [95% CI, 1.16-1.56]) and systemic AD treatment (aOR = 1.27 [95% CI, 1.08-1.50]). Use of soft and hard contact lenses (aOR = 2.15 [95% CI, 1.65-2.80], aOR = 3.35 [95% CI, 1.62-6.92]) were associated with lifetime occurrence of keratitis. Moderate and severe AD, asthma bronchiale and rhinitis were also associated with a higher OSDI level. CONCLUSIONS: This study identified important patient factors associated with OSDs. Clinicians should be attentive of ocular signs and symptoms in AD patients and ask about these.

Patient-reported outcomes from the JADE COMPARE randomized phase 3 study of abrocitinib in adults with moderate-to-severe atopic dermatitis.

BACKGROUND: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. OBJECTIVES: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). METHODS: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. RESULTS: At week 16, the proportion of patients achieving POEM scores <3 was 21.3% and 11.7% for 200 and 100 mg abrocitinib, 12.4% for dupilumab, and 4.8% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.04). Proportion achieving ≥4-point improvement from baseline in NTIS severity was 64.3% and 52.4% for 200 and 100 mg abrocitinib, 54.0% for dupilumab, and 34.4% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.007). Proportion achieving ≥4-point improvement from baseline in DLQI was 85.0% and 74.4% for 200 and 100 mg abrocitinib, 83.4% for dupilumab, and 59.7% for placebo (vs. abrocitinib, P < 0.0001 and P = 0.005). CONCLUSION: Significant improvements in PROs were demonstrated with both abrocitinib doses vs. placebo, and abrocitinib 200 mg provided numerically greater effects compared with dupilumab in patients with moderate-to-severe AD.

Patient perspectives of atopic dermatitis: comparative analysis of terminology in social media and scientific literature, identified by a systematic literature review.

Atopic dermatitis (AD) is a chronic skin disease that significantly impacts patient quality of life (QoL). It is unknown whether patients and physicians have the same interpretation of AD burden. Unmet needs and AD disease burden were evaluated by comparing terminology used in social media with terminology used in scientific literature. AD terminology in social media was identified using the NetBase platform, and natural language processing was performed. Topics and words driving negative sentiment were evaluated overall and in relation to specific symptoms. The systematic review of scientific literature identified publications that included AD and QoL terms was identified from PubMed. Term analysis of titles and abstracts was conducted via natural language processing. The occurrence of topics and co-occurrence of words associated with QoL terms were evaluated. More than 3 million social media mentions (2018-2020) and 1519 scientific publications (2000-2020) were evaluated. There were more negative than positive social media mentions, and flare and pain were common symptoms driving negative sentiment. Face and hands were major drivers of negative sentiment in relation to AD symptoms in social media. Sleep and pain were often mentioned together. In scientific literature, pruritus and depression were the most frequently occurring symptoms. Similarly, pruritus was the most common AD symptom co-occurring with QoL terms in the assessed scientific literature. Social media analyses provide a unique view into the patient experience of AD. Symptoms driving negative sentiment in social media appear to be discordantly represented in scientific literature. Incorporating patient perspectives may improve disease understanding and management.

Care pathways in atopic dermatitis: a retrospective population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment. OBJECTIVE: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD. MATERIALS AND METHODS: This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated. RESULTS: A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age ≥ 12- < 18) and 107 774 adult (age ≥ 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care. CONCLUSIONS: We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.

Systemic treatment of children and adolescents with atopic dermatitis aged ≥2 years: a Delphi consensus project mapping expert opinion in Northern Europe.

BACKGROUND: Paediatric atopic dermatitis (AD) can be burdensome, affecting mental health and impairing quality of life for children and caregivers. Comprehensive guidelines exist for managing paediatric AD, but practical guidance on using systemic therapy is limited, particularly for new therapies including biologics and Janus kinase (JAK) inhibitors, recently approved for various ages in this indication. OBJECTIVES: This expert consensus aimed to provide practical recommendations within this advancing field to enhance clinical decision-making on the use of these and other systemics for children and adolescents aged ≥2 years with moderate-to-severe AD. METHODS: Nineteen physicians from Northern Europe were selected for their expertise in managing childhood AD. Using a two-round Delphi process, they reached full or partial consensus on 37 statements. RESULTS: Systemic therapy is recommended for children aged ≥2 years with a clear clinical diagnosis of severe AD and persistent disease uncontrolled after optimizing non-systemic therapy. Systemic therapy should achieve long-term disease control and reduce short-term interventions. Recommended are cyclosporine A for short-term use (all ages) and dupilumab or methotrexate for long-term use (ages ≥6 years). Consensus was not reached on the best long-term systemics for children aged 2-6 years, although new systemic therapies will likely become favourable: New biologics and JAK inhibitors will soon be approved for this age group, and more trial and real-world data will become available. CONCLUSIONS: This article makes practical recommendations on the use of systemic AD treatments for children and adolescents, to supplement international and regional guidelines. It considers the systemic medication that was available for children and adolescents with moderate-to-severe AD at the time this consensus project was done: azathioprine, cyclosporine A, dupilumab, methotrexate, mycophenolate mofetil and oral glucocorticosteroids. We focus on the geographically similar Northern European countries, whose healthcare systems, local preferences for AD management and reimbursement structures nonetheless differ significantly.

Risk of systemic infections requiring hospitalization in children with atopic dermatitis: a Danish retrospective nationwide cohort study.

BACKGROUND: Infections can trigger worsening of atopic dermatitis (AD). OBJECTIVES: To examine whether hospital-managed paediatric AD is associated with increased risk of extracutaneous infections requiring hospitalization in childhood. METHODS: A nationwide-based cohort study using Danish registries was done. Children aged < 18 years with a hospital diagnosis of AD and children without a hospital diagnosis of AD were sex- and age-matched at date of AD diagnosis. Study outcomes were extracutaneous infections that led to hospitalization. AD severity was defined according to prescriptions for treatments. RESULTS: Of 19 415 children with AD [median follow-up 7·4 years; interquartile range (IQR) 3·3-13.3] and 194 150 without AD (median follow-up 7·7 years; IQR 3·6-13·5), 56% were boys and 50% were aged < 2 years. Children with AD had an increased rate of lower respiratory [LRTI; adjusted hazard ratio (aHR) 1·79, 95% confidence interval (CI) 1·65-1·94)], upper respiratory (URTI; aHR 1·59, 95% CI 1·34-1·88), urinary tract (UTI; aHR 1·34, 95% CI 1·16-1·54), musculoskeletal (MSSI; aHR 1·33, 95% CI 1·06-1·66) and gastrointestinal infections (GITIs; aHR 1·24, 95% CI 1·14-1·35) vs. children without AD. Associations did not clearly vary with AD severity. Absolute risk difference per 10 000 person-years was 26·4 (95% CI 23·0-29·8) for LRTIs, 3·1 (95% CI 1·6-4·7) for URTIs, 3·6 (95% CI 1·8-5·4) for UTIs, 0·9 (95% CI 0·2-2·0) for MSSIs and 8·7 (95% CI 5·7-11·7) for GITIs. CONCLUSIONS: Children with hospital-managed AD have an increased risk of systemic infections that lead to hospitalization; absolute risk is generally low.

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

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