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Background: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)‐13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2‐year impacts of IL‐13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate‐to‐severe AD. Methods: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long‐term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. Results: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL‐37, and S100A8) toward non‐lesional expression. Conclusion: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non‐lesional levels, further highlighting the key role of IL‐13 in the pathogenesis of AD. Clinical Trial Registration: NCT03131648, NCT03587805. [ABSTRACT FROM AUTHOR]

Background: This is the first report on the effects of abrocitinib, a Janus kinase 1–selective inhibitor, on the expression of skin biomarkers in patients with moderate‐to‐severe atopic dermatitis (AD). Methods: JADE MOA (NCT03915496) was a double‐blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once‐daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]‐12), epidermal hyperplasia (keratin‐16 [KRT16]), T‐helper 2 (Th2) immune response (C‐C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks. Results: A total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP‐12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose‐dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26. Conclusions: Alongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Introduction Lebrikizumab is an interleukin (IL)-13 inhibitor that has completed phase 3 studies. It demonstrated statistical superiority vs. placebo in patients with moderate-to-severe atopic dermatitis (AD) across all primary and key secondary endpoints at week 4 and week 16 of ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). Objectives: The objective of this analysis is to determine lebrikizumab's impact on AD-relevant serum biomarkers in patients from these studies through week 16. Methods: Protein biomarkers were determined in available serum samples from patients receiving lebrikizumab 250 mg every 2 weeks (n=72) or placebo (n=36) from both ADvocate1 and ADvocate2. Pre- and post-treatment biomarkers were compared to healthy controls (HC, n=30) which were age, sex, race, and ethnically matched. The analysis included biomarkers known to be elevated in AD. IL-13 was only measured at baseline because of lebrikizumab's known interference with IL-13 measurement. Results: At baseline, CCL13, CCL17, CCL22, total IgE, IL-5, IL-13, and periostin were elevated in patients with AD (p<0.001) with IL-13 measuring approximately 7-fold greater in the AD population vs. HC. In patients with AD, IL-4, CCL11, CXCL10, CCL2, and CCL4 were not elevated at baseline vs. HC.At week 4, lebrikizumab significantly reduced levels of the key type 2 biomarkers, CCL13, CCL17, and periostin vs. placebo (p<0.01) with a trend toward levels consistent with HC (within 1.5-fold). At week 16, CCL13, CCL17, and periostin levels remained consistent with HC levels with CCL13 and periostin retaining statistically significant reductions vs. placebo (p<0.01). Conclusions: In sum, selective targeting of IL-13 with lebrikizumab monotherapy reduced known molecular biomarkers of systemic type 2 inflammation in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction Lebrikizumab is a novel monoclonal antibody that binds with high affinity and slow off-rate to IL-13, thereby blocking the downstream effects of IL-13 with high potency. The efficacy and safety of lebrikizumab have been investigated in a number of Phase 3 trials including: ADvocate1 (NCT04146363), ADvocate2 (NCT04178967), ADhere (NCT04250337), and ADjoin (NCT04392154). Lebrikizumab (with or without TCS) was efficacious in providing clinically meaningful improvements in the signs and symptoms of AD through Week(W) 52 in adult and adolescent patients with moderate-to-severe AD. Objectives: We report the efficacy and safety of lebrikizumab (LEB) in the long-term extension study ADjoin (NCT04392154) following 104 weeks of continuous LEB treatment with and without TCS use. Methods: Patients in ADvocate1&2 who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were re-randomized 2:2:1 to LEB250mg Q2W, LEB250mg Q4W, or placebo (LEB withdrawal). Patients who completed W52 of ADvocate1&2 were able to enroll in ADjoin. Patients in ADhere who achieved either EASI 75 or IGA 0/1 (without rescue) at W16 were able to enroll into ADjoin and randomized 2:1 to LEB250mg Q2W or LEB250mg Q4W. Data are reported for patients originating from ADvocate1&2 and ADhere who received LEB250mg Q2W or Q4W in ADjoin. Efficacy outcomes were assessed based on all collected data (as observed analysis) up to 104W of LEB treatment. Safety was reported from ADjoin enrollment up to the data cut-off April 14, 2023. Results: At W104, IGA 0/1 was maintained by 38/44 (86.4%; Q2W) and 42/55 (76.4%; Q4W) patients from ADvocate1&2 and 26/31 (83.9%; Q2W) and 11/14 (78.6%; Q4W) patients from ADhere. EASI 75 was maintained by 65/68 (95.6%; Q2W) and 77/80 (96.3% Q4W) ADvocate1&2 patients and 39/41 (95.1%; Q2W) and 24/25 (96.0%; Q4W) ADhere patients at W104. In patients who achieved EASI 75 at W16, EASI 90 was achieved by 56/68 (82.4%; Q2W) and 66/80 (82.5%; Q4W) ADvocate1&2 patients and 35/41 (85.4%; Q2W) and 18/25 (72.0%; Q4W) ADhere patients at 104W.During ADjoin, 166/267 (62.2%) patients from the subpopulations of ADvocate1&2 and ADhere who received LEB Q2W or Q4W in ADjoin reported adverse events (AEs), most of which were mild (31.5%, n=84) or moderate (27.0%, n=72) in severity. Serious AEs were reported by 10 (3.8%) patients. There was one death in the ADhere Q2W arm. Six (2.3%) patients reported AEs leading to treatment discontinuation. The safety profile of LEB in ADjoin is consistent with that observed during ADvocate1&2 and ADhere. Conclusions: Efficacy outcomes were maintained long-term, over 2 years of continuous LEB treatment, in both LEB250mg Q2W and Q4W arms. The safety profile of LEB in ADjoin is consistent with previous LEB studies in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction & Objectives: Upadacitinib (UPA) is an oral Janus kinase 1 (JAK1) inhibitor approved in multiple countries for the treatment of adolescents and adults with moderate-to-severe atopic dermatitis (AD). Here, we present the efficacy and safety of UPA administered over 140 weeks in an ongoing randomized, double-blinded, multicenter phase 3 study (Measure Up 1, NCT03569293). Materials & Methods: Patients (12-75 years) with moderate-to-severe AD were randomized 1:1:1 to receive UPA 15 mg (UPA15), UPA 30 mg (UPA30), or placebo (PBO) once daily at baseline. At week 16, PBO-treated patients were re-randomized 1:1 to receive UPA15 (PBO/UPA15) or UPA30 (PBO/UPA30) once daily. Co-primary endpoints were the proportion of patients achieving ≥75% reduction in EASI (EASI 75) from baseline and vIGA-AD of clear (0) or almost clear (1) with ≥2 grades of reduction from baseline (vIGA-AD 0/1) at week 16. A meaningful improvement in itch, defined as a ≥4-point reduction in Worst Pruritus Numeric Rating Scale (ΔWP-NRS≥4), was assessed among patients with baseline WP-NRS≥4. All efficacy endpoints were summarized using the Observed Cases (OC) approach, and no missing data imputation was applied. Safety was assessed by monitoring of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), and treatment-emergent adverse events of special interest (AESI), which were analysed as exposure-adjusted rates per 100 patient-years (PY). Results: Efficacy results were sustained up to week 140 since week 16. Proportions of patients in the UPA15 (205), UPA30 (206), PBO/UPA15 (91), and PBO/UPA30 (94) groups achieving EASI 75 at week 140 were 88.8% (182), 90.3% (186), 83.5% (76), and 89.4% (84), respectively, and for vIGA-AD 0/1 was 63.4% (130), 65.5% (135), 60.4% (55), and 75.5% (71), respectively. Proportions of patients achieving an improvement (reduction) in WP-NRS≥4 from baseline at week 140 were 68.0% (136), 70.5% (146), 71.3% (62), and 81.3% (74) respectively. Overall, the rates of AESIs were similar across treatment groups, which aligned with prior reports at earlier time points. Both UPA15 and UPA30 were well-tolerated in all patients, and no new safety signals were observed compared to the known safety profile of UPA. Data from two additional pivotal studies will be available at the time of presentation. Conclusion: In this interim analysis, sustained skin clearance and itch and a consistent safety profile were observed with UPA 15 mg and UPA 30 mg across 140 weeks in adolescent and adult patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib, an oral, once-daily, Janus kinase 1-selective inhibitor, is efficacious in moderate-to-severe atopic dermatitis with a manageable long-term safety profile. Objective: We aimed to provide updated integrated long-term safety results for abrocitinib from available data accrued up to a maximum of almost 4 years in patients with moderate-to-severe atopic dermatitis from the JADE clinical development program. Methods: Analysis included 3802 patients (exposure: 5213.9 patient-years) from the phase II monotherapy study (NCT02780167) and the phase III studies JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871), JADE TEEN (NCT03796676), JADE COMPARE (NCT03720470), JADE DARE (NCT04345367; 200 mg only), JADE REGIMEN (NCT03627767), and JADE EXTEND (NCT03422822; data cutoff 25 September, 2021). Data from patients receiving one or more doses of abrocitinib 200 mg or 100 mg were pooled in a consistent-dose cohort (patients were allocated to receive the same abrocitinib dose throughout exposure in the qualifying parent study and/or long-term study) or a variable-dose cohort (patients received open-label abrocitinib 200 mg; responders were randomized to abrocitinib 200 mg, 100 mg, or placebo, and could then receive abrocitinib 200 mg plus topical corticosteroids as rescue therapy). Incidence rates of adverse events of special interest were assessed. Cox regression analysis of risk factors for herpes zoster and serious infections was performed. Results: Overall, this safety analysis of long-term data up to a maximum of ~ 4 years of abrocitinib exposure does not indicate any changes from the previously reported risk profile. The most frequent serious infections (per Medical Dictionary for Regulatory Activities preferred term) with consistent-dose abrocitinib 200 mg and 100 mg were herpes zoster (0.5% and 0.2%), pneumonia (0.2% with either dose), and herpes simplex (0.1% with either dose). Risk factors for herpes zoster were a history of herpes zoster, abrocitinib 200-mg dose, age ≥ 65 years, absolute lymphocyte count < 1 × 103/mm3 before the event, and residing in Asia. For serious infections, > 100 kg body weight was a risk factor. Incidence rate/100 patient-years (95% confidence interval) with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in older (aged ≥ 65 years) patients versus younger (aged 18 to < 65 years) patients for serious adverse events (17.6 [11.7‒25.4] vs 6.7 [5.8‒7.8]), malignancy excluding non-melanoma skin cancer (2.4 [0.6‒6.0] vs 0.1 [0.0‒0.4]), non-melanoma skin cancer (2.4 [0.6‒6.1] vs 0.2 [0.1‒0.4]), lymphopenia (3.5 [1.3‒7.6] vs 0.1 [0.0‒0.3]), and venous thromboembolism (1.7 [0.4‒5.1] vs 0.1 [0.0‒0.3]). Incident rate/100 patient-years (95% confidence interval) of non-melanoma skin cancer with the consistent abrocitinib 200-mg and 100-mg dose combined was higher in current/former smokers (0.9 [0.4‒1.6]) vs never-smokers (0.0 [0.0‒0.1]). Conclusions: This safety update showed a consistent profile for abrocitinib with no new safety signals and continues to support that abrocitinib has a manageable long-term safety profile in patients with moderate-to-severe atopic dermatitis. Risk of specific adverse events was higher in certain patient populations, especially those aged ≥ 65 years. [Video abstract available.] Clinical Trial Registration: NCT02780167; study start date: April, 2016; primary completion date: March, 2017; study completion date: April, 2017. NCT03349060; study start date: 7 December, 2017; study completion date: 26 March, 2019. NCT03575871; study start date: 29 June, 2018; study completion date: 13 August, 2019. NCT03720470; study start date: 29 October, 2018; primary completion date: 27 December, 2019; study completion date: 6 March, 2020. NCT03796676; study start date: 18 February, 2019; study completion date: 8 April, 2020. NCT03627767; study start date: 11 June, 2018; primary completion date: 2 September, 2020; study completion date: 7 October, 2020. NCT04345367; study start date: 11 June, 2020; primary completion date: 16 December, 2020; study completion date: 13 July, 2021. NCT03422822; study start date: 8 March, 2018; study completion date: ongoing (estimated completion date: 31 January, 2026). Plain Language Summary: Abrocitinib is an approved treatment for people with moderate or severe atopic dermatitis, also known as AD or atopic eczema. Abrocitinib is a tablet that is taken by mouth once a day. This safety analysis looked at the side effects of treatment in a large group of adults and adolescents with moderate or severe AD who took abrocitinib up to a maximum of almost 4 years. This analysis also looked at which people were more likely to have certain side effects after taking abrocitinib. The results from this analysis were similar to those of previous safety analyses with abrocitinib, with no new side effects. Infections such as shingles, pneumonia, or herpes simplex can occur during treatment with abrocitinib. Shingles was more likely to occur in people who previously had shingles before taking abrocitinib, or who took the higher dose of abrocitinib (200 mg), or were 65 years of age or older, or had certain blood test results, or lived in Asia. People who are 65 years of age or older and took abrocitinib were more likely to develop some types of cancer, have certain abnormal blood test results, or develop blood clots in the veins than people with AD who were younger and took abrocitinib. Current or former smokers with AD who took abrocitinib were more likely to develop skin cancer (but not melanoma) than people with AD who took abrocitinib but have never smoked. This analysis further shows that abrocitinib had manageable safety in patients with moderate-to-severe AD. Dex5AhfAxs29XQspjFnxYi Video abstract: Integrated safety update of abrocitinib in 3802 patients with moderate-to-severe atopic dermatitis: data from more than 5200 patient-years with up to 4 years of exposure (MP4 63720 KB) [ABSTRACT FROM AUTHOR]

Introduction: Tape‐strips, a minimally invasive method validated for the evaluation of several skin diseases, may help identify asthma‐specific biomarkers in the skin of children with allergic asthma. Methods: Skin tape‐strips were obtained and analyzed with RNA‐Seq from children with moderate allergic asthma (MAA) (n = 11, mean age 7.00; SD = 1.67), severe allergic asthma (SAA) (n = 9, mean age 9.11; SD = 2.37), and healthy controls (HCs) (n = 12, mean age 7.36; SD = 2.03). Differentially expressed genes (DEGs) were identified by fold change ≥2 with a false discovery rate <0.05. Transcriptomic biomarkers were analyzed for their accuracy in distinguishing asthma from HCs, their relationships with asthma‐related outcomes (exacerbation rate, lung function‐FEV1, IOS‐R5‐20, and lung inflammation‐FeNO), and their links to skin (barrier and immune response) and lung (remodeling, metabolism, aging) pathogenetic pathways. Results: RNA‐Seq captured 1113 in MAA and 2117 DEGs in SAA. Epidermal transcriptomic biomarkers for terminal differentiation (FLG/filaggrin), cell adhesion (CDH19, JAM2), lipid biosynthesis/metabolism (ACOT2, LOXL2) were significantly downregulated. Gene set variation analysis revealed enrichment of Th1/IFNγ pathways (p <.01). MAA and SAA shared downregulation of G‐protein‐coupled receptor (OR4A16, TAS1R3), upregulation of TGF‐β/ErbB signaling‐related (ACVR1B, EGFR, ID1/2), and upregulation of mitochondrial‐related (HIGD2A, VDAC3, NDUFB9) genes. Skin transcriptomic biomarkers correlated with the annualized exacerbation rate and with lung function parameters. A two‐gene classifier (TSSC4‐FAM212B) was able to differentiate asthma from HCs with 100% accuracy. Conclusion: Tape‐strips detected epithelial barrier and asthma‐associated signatures in normal‐appearing skin from children with allergic asthma and may serve as an alternative to invasive approaches for evaluating asthma endotypes. [ABSTRACT FROM AUTHOR]

Background: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. Methods: Employing single‐cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. Results: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2‐priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. Conclusion: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, heterogeneous, inflammatory disease characterized by skin lesions, pruritus, and pain. Patients with moderate-to-severe AD experience chronic symptoms, intensified by unpredictable flares, and often have comorbidities and secondary complications, which can result in significant clinical burden that impacts the patient's overall quality of life. The complex interplay of immune dysregulation and skin barrier disruption drives AD pathogenesis, of which T-cell-dependent inflammation plays a critical role in patients with AD. Despite new targeted therapies, many patients with moderate-to-severe AD fail to achieve or sustain their individual treatment goals and/or may not be suitable for or tolerate these therapies. There remains a need for a novel, efficacious, well-tolerated therapeutic option that can deliver durable benefits across a heterogeneous AD patient population. Expression of OX40 [tumor necrosis factor receptor superfamily, member 4 (TNFRSF4)], a prominent T-cell co-stimulatory molecule, and its ligand [OX40L; tumor necrosis factor superfamily, member 4 (TNFSF4)] is increased in AD. As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD. [ABSTRACT FROM AUTHOR]

Zusammenfassung: Die atopische Dermatitis (AD) ist die häufigste entzündliche Haut-erkrankung und gilt als komplexe und heterogene Erkrankung. Kürzlich wurden verschiedene AD-Phänotypen beschrieben, die nach dem Alter des Patienten zu Beginn, dem ethnischen Hintergrund, der Krankheitsdauer und anderen Krankheitsmerkmalen definiert wurden und der Notwendigkeit eines personalisierten Behandlungsansatzes zugrunde liegen. Jüngste Fortschritte beim Verständnis der AD-Pathogenese führten zu einer echten translationalen Revolution und zu einer exponentiellen Erweiterung der therapeutischen Pipeline. Die Untersuchung von Biomarkern in klinischen Studien zu neuen Behandlungen trägt dazu bei, die Rolle jedes Zytokins und Immunwegs bei der AD zu klären und wird es ermöglichen, den einzigartigen immunologischen Fingerabdruck jeder AD-Untergruppe zu adressieren. Die personalisierte Medizin wird das ultimative Ziel dieser gezielten translationalen Forschung sein. In dieser Übersichtsarbeit diskutieren wir die Veränderungen in den Konzepten sowohl der Pathogenese als auch des Behandlungsansatzes für AD, heben die wissenschaftliche Begründung für jede zielgerichtete Behandlung hervor und berichten über die neuesten klinischen Daten zur Wirksamkeit. [ABSTRACT FROM AUTHOR]

Background: RPT193 is an orally administered small molecule antagonist of the human C‐C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T‐helper Type 2 (Th2) cells. We investigated single‐ and multiple‐ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate‐to‐severe atopic dermatitis (AD). Methods: This was a first‐in‐human randomized, placebo‐controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate‐to‐severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. Results: In healthy (n = 72) and AD subjects (n = 31), once‐daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment‐emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p <.05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193‐treated versus placebo‐treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. Conclusions: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease. [ABSTRACT FROM AUTHOR]

The article discusses the adoption and use of the vIGA-AD scale, a validated scale for measuring the severity of atopic dermatitis (AD). The scale was developed in 2016 to provide a standardized and representative measure of AD severity. The study analyzed data from ClinicalTrials.gov and PubMed to assess the scale's uptake in the AD research community. The results showed an increase in the proportion of studies and publications using the vIGA-AD scale over the years. The article also highlights the limitations of the scale and suggests using it in combination with other outcome measures. The authors conclude that the vIGA-AD scale has been widely adopted by researchers and sponsors as a validated measure of AD severity. [Extracted from the article]

Treat‐to‐target (T2T) is a pragmatic therapeutic strategy being gradually introduced into dermatology after adoption in several other clinical areas. Atopic dermatitis (AD), one of the most common inflammatory skin diseases, may also benefit from this structured and practical therapeutic approach. We aimed to evaluate existing data regarding the T2T approach in dermatology, with a specific focus on AD, as well as the views of International Eczema Council (IEC) members on the potential application of a T2T approach to AD management. To do so, we systematically searched for peer‐reviewed publications on the T2T approach for any skin disease in the PubMed and Scopus databases up to February 2022 and conducted a survey among IEC members regarding various components to potentially include in a T2T approach in AD. We identified 21 relevant T2T‐related reports in dermatology, of which 14 were related to psoriasis, five to AD, one for juvenile dermatomyositis and one for urticaria. In the IEC member survey, respondents proposed treatable traits (with itch, disease severity and sleep problems getting the highest scores), relevant comorbidities (with asthma being selected most commonly, followed by anxiety and depression in adults), recommended specialists that should define the approach in AD (dermatologists, allergists and primary care physicians were most commonly selected in adults), and applicable assessment tools (both physician‐ and patient‐reported), in both adult and paediatric patients, for potential future utilization of the T2T approach in AD. In conclusion, while the T2T approach may become a useful tool to simplify therapeutic goals and AD management, its foundation in AD is only starting to build. A multidisciplinary approach, including a wide range of stakeholders, including patients, is needed to further define the essential components needed to utilize T2T in AD. [ABSTRACT FROM AUTHOR]

Background: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape‐stripping is a minimally invasive, nonscarring technique to collect skin samples. Methods: To construct a global AD skin transcriptomic profile comparing tape‐strips to whole‐skin biopsies, we performed RNA‐seq on tape‐strips and biopsies taken from the lesional skin of 20 moderate‐to‐severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold‐change (FCH) ≥2.0 and false discovery rate <0.05. Results: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape‐strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape‐strips showed higher FCHs for innate immunity (IL‐1B, IL‐8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL‐13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL‐22, S100As) and dermal cytokines (IFN‐γ, CCL26). Itch‐related genes (IL‐31, TRPV3) were preferentially captured by tape‐strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape‐strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. Conclusions: Tape‐strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD‐related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies. [ABSTRACT FROM AUTHOR]

Circulating skin‐homing cutaneous lymphocyte‐associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL‐13, IL‐31, pruritus, CCL17 and early effects on dupilumab‐treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin‐associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "OX40 in the Pathogenesis of Atopic Dermatitis-A New Therapeutic Target" which appeared in the previous issue of the periodical.