Implementing Federated Analysis using DataSHIELD in the DREAM TO TREAT Atopic Dermatitis Registries Collaboration.

Many new biologic treatments and small molecule agents are emerging and being approved for treating atopic dermatitis (AD). Robust evidence, based on large sample sizes from real-world clinical settings, are needed to investigate the use of these new therapies, However, adequate sample sizes of patient data are difficult to obtain within one country alone, requiring international collaboration and data aggregation. To address this need for cooperative research, we investigated the feasibility for an international collaboration of registries to gather data from real-world clinical settings on patients' use of new systemic treatments for AD by creating a federated network between national registries that enables an analysis environment protecting privacy of information and ensuring compliance with General Data Protection Regulation.

Ultrastrong adhesion to human skin: Calcium as a key regulator of noncovalent interactions.

Calcium is a critical regulator of skin adhesion, stabilizing one of the strongest noncovalent biomolecular interactions ever recorded. Using in vitro and in silico single-molecule force spectroscopy, we demonstrate that calcium ions (Ca) are essential for the ultrastrong binding between the serine-aspartate repeat protein D (SdrD) adhesin and the human skin protein desmoglein-1 (DSG-1), withstanding forces exceeding 2 nanonewtons. Ca ions stabilize both the SdrD complex and the mechanically robust SdrD B-domains, which exhibit unprecedented folding strength.

Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks.

Background: Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD) in adults and adolescents; long-term efficacy and safety data beyond 1 year are needed.

Objective: The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD.

Methods: Measure Up 1 (MeUp1; NCT03569293), Measure Up 2 (MeUp2; NCT03607422), and AD Up (NCT03568318) are ongoing, phase 3, randomized clinical trials evaluating upadacitinib 15 mg (UPA15) and 30 mg (UPA30) in adults and adolescents with moderate-to-severe AD.

Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease.

Introduction: We report the long-term safety of upadacitinib (oral, selective, and reversible Janus kinase inhibitor) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-axSpA), atopic dermatitis (AD), Crohn's disease (CD), and ulcerative colitis (UC).

Methods: Data were analyzed from 16 studies (data cutoff August 15, 2024). Each treatment group was pooled across studies within each indication.

Statement from the frontal fibrosing alopecia international expert alliance: SOFFIA 2024.

Background: As the incidence of frontal fibrosing alopecia (FFA) continues to rise, there is a need for an optimal treatment algorithm for FFA.

Objective: To produce an international consensus statement on the treatment modalities and prognostic indicators of FFA.

Methods: Sixty-nine hair experts from six continents were invited to participate in a three-round Delphi process.

Myeloid and Mast Cell Progenitors Are Elevated in Atopic Dermatitis.

Chronic spontaneous urticaria and atopic dermatitis (AD) are chronic skin disorders characterized by itch. Although mast cells play an integral role in the pathogenesis of chronic spontaneous urticaria, their role in AD is unclear, having a contributory role in a disease largely driven by T helper 2 polarization. Despite this, the role of mast cells in AD is important, given their release of proinflammatory mediators.

Effect of Topical Corticosteroid Treatment on microRNA Expression in Infants with Atopic Dermatitis.

MicroRNAs (miRNAs) have been implicated in a variety of disorders. Although studies have examined miRNA in pediatric atopic dermatitis (AD), the impact of topical corticosteroid (TCS) therapy on miRNA expression in pediatric AD has not been investigated. We sought to investigate the effects of 6 weeks of TCS therapy on miRNA expression in infants with AD.

Methotrexate and ciclosporin both reduce levels of circulating IL-4 and IL-13 expressing CD4+ memory T-cells in childhood atopic dermatitis.

Atopic dermatitis (AD) is a chronic dermatosis characterised by type-2 inflammatory responses, skin barrier anomalies, and microbiome dysregulation. The variation of AD presentation necessitates a better understanding of the underlying disease mechanisms and the modulation of immune markers over a treatment course. Globally the most used systemic therapies for moderate-to-severe AD are methotrexate (MTX) and ciclosporin (CyA).

Toward the Next Generation of In Silico Modeling of Dynamic Host-Microbiota Interactions in the Skin.

Understanding how the skin microbiota contributes to skin health and disease requires knowledge of the dynamic interactions between the skin and its resident microbes. In silico modeling complements in vivo and in vitro experiments by enabling a systems-level understanding of dynamic skin-microbiota interactions. However, the number of published in silico skin microbiota models remains limited.

Towards Personalised Therapy in Chronic Spontaneous Urticaria: Advancing From Endotype to Clinical Response.

Chronic spontaneous urticaria (CSU) is a skin disorder characterised by recurrent hives and swellings that has a profound effect upon quality of life. Current guidelines for the management of CSU outline sequential use of standard dosing nonsedating H1 antihistamines, fourfold dose antihistamines and the anti-IgE monoclonal antibody omalizumab. A proportion of patients will have partial response or no response to omalizumab despite uptitration of dose.

A pan-European register-based observational study of abrocitinib and conventional systemic therapies in moderate and severe atopic dermatitis: the DREAM TO TREAT AD study protocol.

Background: Atopic dermatitis (AD) is a common chronic inflammatory skin condition. Currently, there is a lack of real-world evidence regarding the effectiveness of systemic therapies for moderate-to-severe AD. Abrocitinib is a novel Janus kinase 1 selective inhibitor licensed for AD in adults and adolescents requiring systemic treatment.

Telangiectasia in the Distribution of the Superior Vena Cava: A Novel Dermatological Manifestation of 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes.

Two-Year Efficacy and Safety of Lebrikizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Long-Term Extension (ADjoin).

Introduction: The efficacy and safety of lebrikizumab, a high-affinity monoclonal antibody targeting interleukin-13, were investigated in patients with moderate-to-severe atopic dermatitis (AD) up to 52 weeks in phase 3 trials. This analysis evaluates safety and maintenance of response through 104 weeks of lebrikizumab treatment in patients with moderate-to-severe AD who achieved clinical response with lebrikizumab at week 16.

Methods: ADjoin is a 100-week phase 3 long-term extension study.

Gene-Environment Interaction Affects Risk of Atopic Eczema: Population and In Vitro Studies.

Background: Multiple environmental and genetic factors play a role in the pathogenesis of atopic eczema (AE). We aimed to investigate gene-environment interactions (G × E) to improve understanding of the pathophysiology.

Methods: We analysed data from 16 European studies to test for interaction between the 24 most significant AE-associated loci identified from genome-wide association studies and 18 early-life environmental factors.

Exposure-response of ciclosporin and methotrexate in children and young people with severe atopic dermatitis: a secondary analysis of the TREatment of severe Atopic dermatitis Trial (TREAT).

This is a secondary analysis of a multicentre randomized controlled trial of ciclosporin and methotrexate in children and young people (CYP) with severe atopic dermatitis (AD). Longitudinal trough ciclosporin and erythrocyte methotrexate polyglutamate (MTX-PG) concentrations were measured to evaluate their associations with treatment response and adverse events. Both ciclosporin (4 mg kg-1 daily) and methotrexate (0.

Long-Term Safety of Abrocitinib in Moderate-to-Severe Atopic Dermatitis: Integrated Analysis by Age.

Background: Abrocitinib has a manageable long-term safety profile for patients with moderate-to-severe atopic dermatitis. Identifying populations at higher risk of adverse events will help optimize dose selection.

Objective: To evaluate abrocitinib long-term safety by age.

Integrated Efficacy and Safety Analysis of Abrocitinib in Adolescents With Moderate-to-Severe Atopic Dermatitis.

Background: Abrocitinib has demonstrated long-term efficacy (48 weeks) and safety (~4 years) in adults and adolescents with moderate-to-severe atopic dermatitis (AD). This analysis evaluated abrocitinib efficacy in adolescents through 112 weeks, and safety of up to 4.6 years of exposure.

Lebrikizumab vs Other Systemic Monotherapies for Moderate-to-Severe Atopic Dermatitis: Network Meta-analysis of Efficacy.

Introduction: A systematic literature review and network meta-analysis (NMA) were conducted to compare the short-term efficacy of lebrikizumab to other biologic and Janus kinase (JAK) inhibitor monotherapies approved for moderate-to-severe atopic dermatitis in adults and adolescents.

Methods: The NMA included randomized, double-blind, placebo-controlled monotherapy phase 2 and 3 trials of biologics (lebrikizumab 250 mg every 2 weeks [Q2W], dupilumab 300 mg Q2W, and tralokinumab 300 mg Q2W) and JAK inhibitors (abrocitinib 100/200 mg daily, baricitinib 2/4 mg daily, and upadacitinib 15/30 mg daily) at approved doses. Efficacy outcomes included the proportions of patients achieving Eczema Area and Severity Index (EASI) improvement, an Investigator Global Assessment of 0 or 1 (IGA 0/1), and a ≥ 4-point improvement in pruritus/itch numeric rating scale score at 12 weeks (abrocitinib) or 16 weeks (other treatments).

Orismilast, a phosphodiesterase 4B/D inhibitor, in moderate-to-severe atopic dermatitis: efficacy and safety from a multicentre randomized placebo-controlled phase IIb dose-ranging study (ADESOS).

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous skin lesions and pruritus. There is an unmet need for effective first-line systemic treatments with good safety profiles, particularly oral medications. Orismilast is a novel first-in-class oral phosphodiesterase 4 (PDE4) B/D inhibitor under investigation for the treatment of moderate-to-severe AD.

Highly accurate, noninvasive early identification of infants with a filaggrin loss-of-function mutation by in vivo Raman spectroscopy, followed from birth to 12 months.

Background: Loss-of-function FLG mutation (FLGmut) carriers are at an increased risk of developing atopic dermatitis (AD), characterized by earlier onset and more severe disease. AD is driven by a complex interplay between skin barrier function, T2 and T2-dominant immune dysregulation, and dysbiosis. Results from the Short-Term Topical Application for Prevention of Atopic Dermatitis study suggest 2 early initiating AD pathogenetic pathways: an FLGmut-related skin barrier deficiency pathway and an immune function-related inflammatory pathway.

Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab.

In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck.