Project description:BackgroundThe evidence for systemic treatments for severe childhood eczema is limited and largely based on extrapolation of data from adult studies. Current therapies are often immunosuppressant and may be associated with both short- and long-term side effects. There is increasing in vitro and murine-model evidence for the role of IgE in the immunopathogenesis of atopic eczema. The aim of the study is to assess whether anti-IgE treatment (omalizumab) improves eczema, compared to placebo.Methods/designThe Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT) is a randomised, double-blind, placebo-controlled study assessing the role of anti-IgE in the management of severe paediatric eczema. Children with severe atopic eczema, with an objective SCORing Atopic Dermatitis (SCORAD) score of over 40 will be recruited. These children are candidates for systemic therapy, have failed systemic therapy or have experienced side effects from systemic therapy. Sixty-two patients aged between 4 and 19 years will receive anti-IgE for 6 months. The primary outcome measure will be the validated eczema score, the objective SCORAD at 24 weeks. This study has 90% power to detect a 33% relative reduction in SCORAD between active and placebo groups, with 5% significance.DiscussionIgE may have a role to play in eczema, particularly in childhood. This forms the basis for the hypothesis that anti-IgE may be an effective treatment in this patient population. This will be the largest study to evaluate the efficacy of anti-IgE (omalizumab) versus placebo in children with severe eczema. The findings will help to clarify the role of anti-IgE as a potential treatment option in patients with severe childhood eczema.Trial registrationEuropean Clinical Trials Database (EudraCT) Number: 2010-020841-29 . Assigned on 14 May 2010. ISRCTN Registry, Identifier: ISRCTN15090567 . Retrospectively assigned on 3 December 2014. ClinicalTrials.gov, Identifier: NCT02300701 . First received 21 November 2014.

Project description:ImportanceSystemic treatments for severe childhood atopic dermatitis have limited evidence and/or are unlicensed. Despite the efficacy of anti-IgE medication (omalizumab) in the treatment of atopy, no large randomized studies in childhood atopic dermatitis have been published.ObjectiveTo determine the effectiveness of omalizumab in treating severe atopic dermatitis in children.Design, setting, and participantsThe Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT) was a 24-week single-center, double-blind, placebo-controlled randomized clinical trial with a 24-week follow-up. Conducted from November 20, 2014, to August 31, 2017, at Guy's and St Thomas' Hospital NHS Foundation Trust and King's College London in the United Kingdom, this trial recruited participants after a screening visit. Eligible participants (n = 62) were aged 4 to 19 years and had severe eczema (with objective Scoring Atopic Dermatitis [SCORAD] index >40) that was unresponsive to optimum therapy. Statistical analysis was conducted using the intention-to-treat principle.InterventionsSubcutaneous omalizumab or placebo for 24 weeks. The drug manufacturer's dosing tables were used to determine the dosage based on total IgE (30-1500 IU/mL) and body weight (in kilograms) at randomization.Main outcomes and measuresObjective SCORAD index after 24 weeks of treatment.ResultsIn total, 62 children (mean [SD] age, 10.3 [4.2] years; 32 (52%) were male) were randomized to either omalizumab (n = 30) or placebo (n = 32). Five participants withdrew from treatment (4 [13%] from the placebo group, and 1 [3%] from the omalizumab group). Follow-up attendance was 97% at week 24 and 98% at week 48. After adjustment for baseline objective SCORAD index, age, and IgE level, the mean difference in objective SCORAD index improvement between groups at week 24 was -6.9 (95% CI, -12.2 to -1.5; P = .01), significantly favoring omalizumab therapy and reflecting the results in other assessments of atopic dermatitis severity. Improved quality-of-life scores were seen in the omalizumab group, as measured by the Children's Dermatology Life Quality Index/Dermatology Life Quality Index (-3.5; 95% CI, -6.4 to -0.5) and Pediatric Allergic Disease Quality of Life Questionnaire score (-0.5; 95% CI, -0.9 to -0.0). Improvements in disease severity occurred despite lower potent topical corticosteroid use in the omalizumab group compared with the placebo group (median [interquartile range (IQR)] percentage of body surface area covered, 16% [10%-46%] vs 31% [14%-55%]; median [IQR] number of days of use, 109 [34-164] days vs 161 [82-171] days).Conclusions and relevanceThis randomized clinical trial found that omalizumab significantly reduced atopic dermatitis severity and improved quality of life in a pediatric population with atopy and severe eczema despite highly elevated total IgE levels at baseline. The result was associated with a potent topical corticosteroid sparing effect and may suggest that omalizumab is a treatment option for difficult-to-manage severe eczema in children with atopy.Trial registrationClinicalTrials.gov identifier: NCT02300701.

Project description:Background: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Results: We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusion: Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Skin biopsies from normal ('normal') and lesional and patch-tested ('leisonal') skin from Atopic eczema patients sensitized to Malassezia sympodialis Organism Part: location of skin biopsy Keywords: disease state analysis

Project description:Background: Atopic eczema (AE) is a common chronic inflammatory skin disorder. In order to dissect the genetic background several linkage and genetic association studies have been performed. Yet very little is known about specific genes involved in this complex skin disease, and the underlying molecular mechanisms are not fully understood. Results: We used human DNA microarrays to identify a molecular picture of the programmed responses of the human genome to AE. The transcriptional program was analyzed in skin biopsy samples from lesional and patch-tested skin from AE patients sensitized to Malassezia sympodialis (M. sympodialis), and corresponding biopsies from healthy individuals. The most notable feature of the global gene-expression pattern observed in AE skin was a reciprocal expression of induced inflammatory genes and repressed lipid metabolism genes. The overall transcriptional response in M. sympodialis patch-tested AE skin was similar to the gene-expression signature identified in lesional AE skin. In the constellation of genes differentially expressed in AE skin compared to healthy control skin, we have identified several potential susceptibility genes that may play a critical role in the pathological condition of AE. Many of these genes, including genes with a role in immune responses, lipid homeostasis, and epidermal differentiation, are localized on chromosomal regions previously linked to AE. Conclusion: Through genome-wide expression profiling, we were able to discover a distinct reciprocal expression pattern of induced inflammatory genes and repressed lipid metabolism genes in skin from AE patients. We found a significant enrichment of differentially expressed genes in AE with cytobands associated to the disease, and furthermore new chromosomal regions were found that could potentially guide future region-specific linkage mapping in AE. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied. Disease State: Skin biopsies from normal ('normal') and lesional and patch-tested ('leisonal') skin from Atopic eczema patients sensitized to Malassezia sympodialis Organism Part: location of skin biopsy Keywords: disease state analysis Computed

Dataset Information

The role of anti-IgE (omalizumab/Xolair) in the management of severe recalcitrant paediatric atopic eczema (ADAPT): statistical analysis plan.

Publications

The role of anti-IgE (omalizumab/Xolair) in the management of severe recalcitrant paediatric atopic eczema (ADAPT): statistical analysis plan.

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