Search

Additionally, occurrence of both AD eyelid involvement and AD facial involvement in the past year was significantly higher in patients with moderate-to-severe OSD compared to patients with no or mild OSD ( I n i = 28 (90.3%) vs. I n i = 18 (46.2%), I p i = <.001 and I n i = 31 (100.0%) vs. I n i = 33 (84.6%), I p i = .030 respectively). Keywords: atopic dermatitis; goblet cell; ocular surface disease EN atopic dermatitis goblet cell ocular surface disease 801 805 5 06/01/22 20220601 NES 220601 Key Messages In a single-centre study, we assessed ocular surface disease prevalence in moderate-to-severe atopic dermatitis. Diagnosing OSD is important since it may be associated with chronic limbitis, possibly leading to irreversible limbal stem cell deficiency and subsequently to irreversible long-term visual loss.3 In our study, lower conjunctival GCD was found in patients with OSD, compared to patients without OSD. However, by comparing GCD of patients with OSD to GCD of healthy controls described in the literature, we can conclude that moderate-to-severe AD patients with OSD have lower GC counts. [Extracted from the article]

Increasing evidence shows that pediatric atopic dermatitis (AD) differs from adult AD on a biologic level. Broad biomarker profiling across a wide range of ages of pediatric patients with AD is lacking. Our aim was to identify serum biomarker profiles in children with AD aged 0 to 17 years and compare these profiles with those previously found in adults with AD. Luminex multiplex immunoassays were used to measure 145 biomarkers in serum from 240 children with AD (aged 0-17 years). Principal components analysis followed by unsupervised k-means clustering were performed to identify patient clusters. Patients were stratified into age groups (0-4 years, 5-11 years, and 12-17 years) to assess association between age and cluster membership. Children aged 0 to 4 years had the highest levels of T H 1 cell–skewing markers and lowest levels of T H 17 cell–related markers. T H 2 cell–related markers did not differ significantly between age groups. Similar to the pattern in adults, cluster analysis identified 4 distinct pediatric patient clusters (T H 2 cell/retinol–dominant, skin-homing–dominant, T H 1 cell/T H 2 cell/T H 17 cell/IL-1–dominant, and T H 1 cell/IL-1/eosinophil–inferior clusters). Only the T H 1 cell/T H 2 cell/T H 17 cell/IL-1–dominant cluster resembled 1 of the previously identified adult clusters. Although no association with age or age of onset seemed to be found, disease severity was significantly associated with the skin-homing–dominant cluster. Four distinct patient clusters based on serum biomarker profiles could be identified in a large cohort of pediatric patients with AD, of which 1 was similar to previously identified adult clusters. The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define pediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches. [ABSTRACT FROM AUTHOR]

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface disease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupilumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30-11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis. [ABSTRACT FROM AUTHOR]

Median goblet cell density was 2.6 cells/mm (IQR 1.1-4.0) in patients compared to 4.1 cells/mm and 9.8 cells/mm in HCs (Table S1b). Conjunctival inflammation in dupilumab-treated atopic dermatitis comprises a multicellular infiltrate with elevated T1/T17 cytokines: A case series study Composite images derived from Imaging Mass Cytometry of conjunctival biopsy samples from AD patients developing conjunctivitis during dupilumab treatment. [Extracted from the article]

Dupilumab treatment improves signs, symptoms, and quality of life in patients with moderate-to-severe atopic dermatitis. This study evaluated the impact of dupilumab treatment on absenteeism, presenteeism, and related costs in a large multi-centre cohort of adult patients with difficult-to-treat atopic dermatitis in daily practice. Patients treated with dupilumab participating in the Dutch BioDay Registry reporting employment were included. Absenteeism, presenteeism, and related costs at baseline and during follow-up were calculated using the Work Productivity and Activity Impairment questionnaire. A total of 218 adult patients with moderate-to-severe atopic dermatitis were included. Total work impairment reduced significantly from baseline (35.5%) to week 52 (11.5%), p < 0.001. Median weekly productivity losses reduced significantly from baseline (€379.8 (140.7-780.8)) to week 52 (€0.0 (0.0-211.0), p < 0.001). In this study, dupilumab treatment demonstrated a significant improvement in work productivity and reduction in associated costs in a large cohort of patients with difficult-to-treat atopic dermatitis in daily practice. [ABSTRACT FROM AUTHOR]

Background: Real-life data on long-term effectiveness and safety of dupilumab in atopic dermatitis patients are limited.Objective: To study 52-week effectiveness and safety of dupilumab in a prospective multicenter cohort of adult patients with treatment-refractory atopic dermatitis.Methods: Patients treated with dupilumab and participating in the Dutch BioDay registry were included. Clinical effectiveness and safety were evaluated.Results: Two hundred ten atopic dermatitis patients were included. Mean percentage change in Eczema Area and Severity Index score after 16 weeks was -70.0% (standard deviation 33.2%) and further decreased to -76.6% (standard deviation 30.6%) by week 52. A greater than or equal to 75% improvement in the score was achieved by 59.9% of individuals by week 16 and by 70.3% by week 52. The most reported adverse effect was conjunctivitis (34%). Limited patients (17; 8.1%) discontinued dupilumab treatment.Limitations: Because of the lack of a control group and observational design, factors of bias may have been induced.Conclusion: Treatment with dupilumab resulted in a rapid improvement in clinical outcome measures, and effectiveness further improved during the 52-week follow-up period. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a highly heterogeneous disease, both clinically and biologically, whereas patients are still being treated according to a "one-size-fits-all" approach. Stratification of patients into biomarker-based endotypes is important for future development of personalized therapies. Our aim was to confirm previously defined serum biomarker-based patient clusters in a new cohort of patients with AD. A panel of 143 biomarkers was measured by using Luminex technology in serum samples from 146 patients with severe AD (median Eczema Area and Severity Index = 28.3; interquartile range = 25.2-35.3). Principal components analysis followed by unsupervised k-means cluster analysis of the biomarker data was used to identify patient clusters. A prediction model was built on the basis of a previous cohort to predict the 1 of the 4 previously identified clusters to which the patients of our new cohort would belong. Cluster analysis identified 4 serum biomarker–based clusters, 3 of which (clusters B, C, and D) were comparable to the previously identified clusters. Cluster A (33.6%) could be distinguished from the other clusters as being a "skin-homing chemokines/IL-1R1–dominant" cluster, whereas cluster B (18.5%) was a "T H 1/T H 2/T H 17-dominant" cluster, cluster C (18.5%) was a "T H 2/T H 22/PARC-dominant" cluster, and cluster D (29.5%) was a "T H 2/eosinophil-inferior" cluster. Additionally, by using a prediction model based on our previous cohort we accurately assigned the new cohort to the 4 previously identified clusters by including only 10 selected serum biomarkers. We confirmed that AD is heterogeneous at the immunopathologic level and identified 4 distinct biomarker-based clusters, 3 of which were comparable with previously identified clusters. Cluster membership could be predicted with a model including 10 serum biomarkers. [ABSTRACT FROM AUTHOR]

Introduction: Dupilumab has recently been approved for the treatment of moderate to severe atopic dermatitis (AD) in adults. Daily practice data on dupilumab treatment are scarce. Objective: To study the effect of 16‐week treatment with dupilumab on clinical response and serum biomarkers in adult patients with moderate‐severe AD in daily practice. Methods: Data were extracted from the BioDay registry, a prospective multicenter registry. Sixteen‐week clinical effectiveness of dupilumab was expressed as number of patients achieving EASI‐50 (Eczema Area and Severity Index) or EASI‐75, as well as patient‐reported outcomes measures (Patient‐Oriented Eczema Measure, Dermatology Life Quality Index, Numeric Rating Scale pruritus). Twenty‐one biomarkers were measured in patients treated with dupilumab without concomitant use of oral immunosuppressive drugs at five different time points (baseline, 4, 8, 12, and 16 weeks). Results: In total, 138 patients treated with dupilumab in daily practice were included. This cohort consisted of patients with very difficult‐to‐treat AD, including 84 (61%) patients who failed treatment on ≥2 immunosuppressive drugs. At week 16, the mean percent change in EASI score was 73%. The EASI‐50 and EASI‐75 were achieved by 114 (86%) and 82 (62%) patients after 16 weeks of treatment. The most reported side effect was conjunctivitis, occurring in 47 (34%) patients. During dupilumab treatment, disease severity‐related serum biomarkers (TARC, PARC, periostin, and IL‐22), eotaxin‐1, and eotaxin‐3 significantly decreased. Conclusion: Treatment with dupilumab significantly improved disease severity and decreased severity‐related serum biomarkers in patients with very difficult‐to‐treat AD in a daily practice setting. [ABSTRACT FROM AUTHOR]

Combining these eight biomarkers in a biomarker signature increased the capacity to predict treatment responses in severe AD patients. Our results imply that pathophysiological heterogeneity in immunological pathways might underlie differences in treatment responses, and may be used to distinguish a specific subpopulation of difficult-to-treat AD patients in need of systemic treatment from patients who can be controlled with topical therapy. This signature might serve as a valuable addition to the decision whether to start systemic therapy or not in individual AD patients, and the statistical algorithm used in this study may also be applied to construct biomarker signatures predicting treatment response to systemic immunosuppressive drugs, dupilumab or other therapies in the future. Since more targeted therapies will play an increasingly important role in AD treatment, prediction of treatment response can significantly contribute to selecting the right treatment for the right patient. [Extracted from the article]

The article offers a study predicting disease severity in atopic dermatitis (AD) patients treated with cyclosporin A (CsA). Topics include patients with AD, treated with CsA were included; assessed by Eczema Area and Severity Index (EASI) and serum collected before start of CsA; study showed two patients have notable discrepancies between EASI and predicted EASI scores; and study demonstrates that p‐EASI consisting on serum biomarkers predicts disease severity in AD patients.

EASI p-EASI: Predicting disease severity in atopic dermatitis patients treated with dupilumab using a combination of serum biomarkers Keywords: atopic dermatitis; biologics; biomarkers EN atopic dermatitis biologics biomarkers 3287 3289 3 12/03/20 20201201 NES 201201 During the past decade, new more targeted therapies for the treatment of atopic dermatitis (AD) have been developed and are currently under investigation in clinical trials. As few patients did show a quick drop in sIL-2R, extending the current model to a larger patient population including different phenotypes of AD might identify subtypes of AD patients in whom sIL-2R is an important marker. [Extracted from the article]

Background Atopic dermatitis (AD) is a complex, chronic, inflammatory skin disease with a diverse clinical presentation. However, it is unclear whether this diversity exists at a biological level. Objective We sought to test the hypothesis that AD is heterogeneous at the biological level of individual inflammatory mediators. Methods Sera from 193 adult patients with moderate-to-severe AD (six area, six sign atopic dermatitis [SASSAD] score: geometric mean, 22.3 [95% CI, 21.3-23.3] and 39.1 [95% CI, 37.5-40.9], respectively) and 30 healthy control subjects without AD were analyzed for 147 serum mediators, total IgE levels, and 130 allergen-specific IgE levels. Population heterogeneity was assessed by using principal component analysis, followed by unsupervised k-means cluster analysis of the principal components. Results Patients with AD showed pronounced evidence of inflammation compared with healthy control subjects. Principal component analysis of data on sera from patients with AD revealed the presence of 4 potential clusters. Fifty-seven principal components described approximately 90% of the variance. Unsupervised k-means cluster analysis of the 57 largest principal components delivered 4 distinct clusters of patients with AD. Cluster 1 had high SASSAD scores and body surface areas with the highest levels of pulmonary and activation-regulated chemokine, tissue inhibitor of metalloproteinases 1, and soluble CD14. Cluster 2 had low SASSAD scores with the lowest levels of IFN-α, tissue inhibitor of metalloproteinases 1, and vascular endothelial growth factor. Cluster 3 had high SASSAD scores with the lowest levels of IFN-β, IL-1, and epithelial cytokines. Cluster 4 had low SASSAD scores but the highest levels of the inflammatory markers IL-1, IL-4, IL-13, and thymic stromal lymphopoietin. Conclusion AD is a heterogeneous disease both clinically and biologically. Four distinct clusters of patients with AD have been identified that could represent endotypes with unique biological mechanisms. Elucidation of these endotypes warrants further investigation and will require future intervention trials with specific agents, such as biologics. [ABSTRACT FROM AUTHOR]