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Atopic dermatitis (AD) is a common, chronic, and recurrent inflammatory skin condition that affects a considerable portion of the population, and is particularly prevalent among children. The development of AD is influenced by environmental and genetic factors, which cause epidermal barrier dysfunction, immune dysregulation, and dysbiosis. In immune dysregulation, there is excessive production of cytokines. Among the cytokines, interleukin (IL)-13 plays a major role in the pathogenesis of AD. Searching for new and more selective treatments for moderate-to-severe cases is important because of the considerable effect of AD on the quality of life. Tralokinumab and lebrikizumab are selective IL-13 inhibitors that have demonstrated safety and efficacy as treatment options for AD in phase III trials. Tralokinumab is approved for use in Europe and the USA, while lebrikizumab is approved only in Europe. Cendakimab, which is another IL-13 selective inhibitor, has shown promising results in phase II trials, providing safe and effective outcomes. Eblasakimab, which disrupts IL-13 and IL-4 signaling pathways, is currently in phase II trials following well-tolerated administration in phase I studies. This narrative review aims to outline the current state of knowledge regarding the effectiveness and safety of these four biologic agents targeting IL-13 signaling., Competing Interests: Declaration of conflicting interestOrhan Yilmaz, Carlos Teixeira, and Diana Bernardo declare that there is no conflict of interest. Tiago Torres has received consultancy and/or speaker’s honoraria from and/or participated in clinical trials sponsored by AbbVie, Amgen, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Fresenius-Kabi, Janssen, LEO Pharma, Eli Lilly, MSD, Mylan, Novartis, Pfizer, Samsung-Bioepis, Sanofi-Genzyme, Sandoz, and UCB.

Background: The complexity, high prevalence, and substantial personal and socioeconomic burden collectively render atopic dermatitis (AD) a major public health concern. Using crowdsourced Internet data has the potential to provide unique insights into this concern, as demonstrated by several previous studies. However, a comprehensive comparison across European countries remains lacking., Objectives: The study aimed to investigate AD-related web searches across Europe to assess spatiotemporal variations and associations between disease-related and external factors., Methods: AD-related web search data were extracted for 21 European countries between February 2019 and January 2023. Descriptive analysis and autocorrelation functions were performed to examine spatiotemporal patterns. Correlations (r) were used to evaluate the associations between web searches and disease-related, socioeconomic and meteorological data., Results: Over 241 million AD-related web searches were identified, with search volume varying substantially among European countries (p < 0.001) and correlating with AD prevalence and disease burden (both r = 0.51, p = 0.019). Search volume increased between 2019 and 2023 in all countries and seasonally peaked in January and March. Negative correlations with median population age (r = -0.46, p = 0.039), number of general practitioners (r = -0.29, p = 0.226) and specialists (r = -0.27, p = 0.270) were observed. Moderate to strong correlations were found between search volume and cold, humid and windy weather with fewer sunshine hours, while higher online interest typically occurred 1-3 months after such weather conditions., Conclusion: The study highlights the great potential of online crowdsourced data analysis, for example, to investigate the impact of climate change or to identify unmet needs at a population level. Furthermore, the growing online interest in AD and the corresponding seasonal peaks emphasize the necessity of adapting treatment plans, intensifying public health campaigns, and disseminating reliable online information by governments and healthcare providers, especially during these periods., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Abrocitinib is an oral small molecule which selectively inhibits JAK1, modulating multiple cytokine pathways involved in atopic dermatitis. Both abrocitinib 200 mg and 100 mg reached efficacy results comparable to dupilumab and superior to placebo. Abrocitinib 200 mg was superior to dupilumab in some trials, consistently providing a faster response and itch relief from week 2 to 26. Continuous abrocitinib 200 mg is the most effective at controlling this disease, but with an induction-maintenance approach with abrocitinib 200 mg followed by 100 mg, over 55% of patients did not flare for 40 weeks. Abrocitinib common adverse effects are nonserious. A self-limited dose-related decrease in platelet counts was consistently observed, without clinical repercussion. Abrocitinib demonstrated high efficacy and a favorable safety profile.

Atopic dermatitis (AD) is a common, heterogeneous, inflammatory skin disorder characterized by chronic or relapsing eczematous lesions with intense pruritus and discomfort. Affected patients often experience significant impairment in their quality of life, and the treatment of moderate-to-severe AD forms remains challenging. In the past few decades, increasing knowledge on the AD pathogenesis has driven the development of novel targeted therapies. Interleukin (IL)-13 plays a central and pleiotropic role in AD pathogenesis, contributing directly or indirectly to epidermal barrier disfunction, type-2 inflammation, dysbiosis, fibrosis, and itch response. For this reason, agents selectively targeting IL-13, such as lebrikizumab, emerged as a potential therapy for AD. This article reviews the current evidence about lebrikizumab in the management of AD. The phase II and phase III trials seem to corroborate efficacy of lebrikizumab in the treatment of moderate-to-severe AD, as shown by significant improvement of Eczema Area and Severity Index, body surface area, and pruritus scores. Also, lebrikizumab demonstrated favorable safety and tolerability profiles, with the majority of patients experiencing no significant adverse events. Lebrikizumab seems to be a promising emerging targeted biological agent for patients with moderate-to-severe AD. More data on the long-term efficacy and safety, head-to-head comparisons with other agents, and real-world evidence will help to clarify its place in therapy in AD., (© 2023. The Author(s).)

Background: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce., Research Design and Methods: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts., Results: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16., Conclusions: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

Purpose of Review: This review aims to provide a summary of current knowledge on new topical and oral non-biological therapies recently approved for Atopic Dermatitis (AD) treatment., Recent Findings: The immense research carried out in the last decade has focused on understanding the molecular basis underlying AD and has allowed the development of new targeted drugs. Despite several biologic therapies are approved or in development, other non-biologic targeted therapies (small molecules) have emerged, such as the Janus kinase (JAK) inhibitors baricitinib, upadacitinib and abrocitinib, expanding the range of therapeutic options. Based on recent available data from head-to-head comparisons and meta-analysis studies, JAK inhibitors showed a faster onset of action and slightly higher efficacy at 16 weeks compared with biologic agents. Concerning topical treatment, presently, corticosteroids and calcineurin inhibitors are the main therapeutic options, but are not recommended for long-term management due to potential safety issues. Currently, two topical JAK inhibitors (ruxolitinib and delgocitinib) and one phosphodiesterase 4 (PDE4) inhibitor (difamilast) are approved and have shown good efficacy results and a favorable safety profile., Summary: These new drugs (systemic and topical) are needed to increase the success of AD treatment, particularly for patients who do not or no longer respond to treatment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is associated with long-term efficacy and safety issues. Therefore, new topical therapies with different mechanisms of action are required to overcome the limitations of existing treatments. Difamilast is a phosphodiesterase 4 inhibitor currently in phase 3 studies. Difamilast shows antipruritic and anti-inflammatory properties and a rapid onset of action, with significant differences in some parameters from the vehicle within 1 week of treatment. Phase 2 and 3 clinical trials have shown that difamilast ointments are effective and well tolerated in adult and pediatric patients with AD, and are expected to be used for long-term AD treatment. In 2021, difamilast was the first phosphodiesterase 4inhibitor to acquire manufacturing and marketing approval in Japan for the treatment of adult and pediatric patients (2 years of age and older) with AD. This article is a narrative review of the current literature on difamilast in the management of AD.

Introduction: Atopic dermatitis (AD) is a difficult-to-treat inflammatory skin disease with a high impact on patients' quality of life. Dupilumab, an IL-4 and IL-13 inhibitor, was the first monoclonal antibody approved for the treatment of moderate-to-severe AD and is currently approved in patients aged 6 or older., Methods: This is a nationwide, multicenter, retrospective, 48-week study designed by the Portuguese Group of AD to assess real-world efficacy and safety of dupilumab for the treatment of AD., Results: A total of 169 patients were enrolled, with a mean disease duration of 22.75 (±11.98) years. The percentage of patients achieving an improvement of at least 75% in Eczema Area and Severity Index (EASI) compared to baseline (EASI75 response) at weeks 12 and 48 was 67.6% and 74.1%, respectively. In the same timepoints, 25.0% and 44.1% achieved an EASI90 response. Patient-reported outcome measures also improved throughout the study period. Regarding safety, 32.0% of the patients developed adverse events, with conjunctivitis (26.6%), persistent facial erythema (4.7%), and arthritis/arthralgia (3.6%) as the more frequently reported., Conclusion: Data from real-world populations are crucial to guide clinicians in their daily decisions. This study provides data demonstrating that dupilumab is an effective and safe therapeutic option for AD.

Atopic dermatitis is a common, chronic and recurrent inflammatory skin disease, which often appears in childhood but can last into adulthood. It negatively impacts patients, their families and society in general. There is a therapeutic unmet need, with patients requiring new drugs that are safe and effective. The increasing knowledge of the pathophysiology of AD and the role of the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway in the development and maintenance of AD, has led to the development of agents blocking this intracellular signaling pathway, the JAK inhibitors. Baricitinib shows high selectivity for JAK1 and JAK2, making it appealing for the treatment of this condition. Phase II and phase III trials evaluated the efficacy and safety of baricitinib in the treatment of AD, and the results have been encouraging, showing a good efficacy and a favorable safety and tolerability profile. At the end of 2020, EMA approved baricitinib for the treatment of adult patients with moderate-to-severe atopic dermatitis who are candidates for systemic therapy, increasing the therapeutic option for this debilitating disease.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory cutaneous disease. AD is characterized by intense pruritus and enormous clinical heterogeneity. Treatment goals are to improve skin lesions and minimize exacerbations and symptom burden. Currently, topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) are still considered the main topical therapies in disease treatment. However, despite being very effective, TCS and TCI are not recommended for continuous long-term use, due to potential safety issues. Although research in AD has focused primarily on systemic drugs, more than 20 new topical compounds are under development to treat the disease. This review aims to provide a synthesized summary of the current knowledge about AD topical treatment, echoing existing gaps and coming research trends. The available data seems promising, with some drugs already approved (ruxolitinib being the most recent), and several are in an advanced stage of development and will soon be available for treatment of mild to moderate disease, namely tapinarof, difamilast, and roflumilast. However, longer and larger prospective studies are needed to assess the long-term efficacy and safety of these new compounds and evaluate their benefits over current treatments., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Atopic dermatitis (AD) is a relapsing or chronic heterogeneous inflammatory skin disorder with a substantial economic and social impact. AD is a multifactorial disease regulated by a diverse set of environmental and genetic determinants. The main factors involved in the pathogenesis of AD are epidermal barrier dysfunction, immune dysregulation, and dysbiosis. Current data have valued interleukin (IL)-13 as conceivably the crucial cytokine in the underlying inflammation of AD. Advances in understanding AD pathophysiology have driven the progress of targeted immunomodulatory treatments for the treatment of AD, including tralokinumab, a selective IL-13 inhibitor. A phase IIb clinical trial showed that a dosing regimen of 150 or 300 mg every 2 weeks effectively treated moderate-to-severe AD in adults with an acceptable tolerability profile. Phase III clinical trials demonstrated that results with tralokinumab in monotherapy were superior to those with placebo at 16 weeks of treatment. It was also well tolerated up to 52 weeks in the vast majority of patients. In addition, in association with topical corticosteroids, tralokinumab was well tolerated and effective and had a favorable risk-benefit profile. These data provide additional evidence that IL-13 is central to AD pathogenesis, suggesting that tralokinumab may be seen as an innovative option for the treatment of moderate-to-severe AD., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Atopic dermatitis is a common, chronic, immune-mediated disease associated with several comorbidities. Elevated levels of T helper (Th)2, Th22, and also some Th1 and Th17 cytokines are found in atopic dermatitis skin lesions. Similar to psoriasis, there is a tendency towards increased use of more targeted therapies. However, there are still several unmet needs in the treatment of atopic dermatitis concerning long-term efficacy, tolerability, safety, route of administration, and cost. The increased knowledge of atopic dermatitis pathogenesis and the role of Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways has allowed the development of new compounds to inhibit this intracellular signaling pathway implicated in atopic dermatitis-related immune responses. Currently, JAK inhibitors are an important focus of therapeutic research for atopic dermatitis. Upadacitinib and abrocitinib are oral small molecules that inhibit the JAK/STAT pathway by selectively blocking JAK1. Data from phase II and III trials are encouraging, revealing that JAK1 inhibitors are effective and well-tolerated agents for moderate-to-severe atopic dermatitis. Selective JAK1 inhibitors may represent an important therapeutic option to be included in the treatment algorithm of atopic dermatitis, owing to oral administration and a favorable safety and tolerability profile. In this article, we review the current evidence on the efficacy and safety of oral selective JAK1 inhibitors for the treatment of atopic dermatitis.

Background: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset., Objectives: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting., Methods: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia., Conclusions: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations., (© 2019 British Association of Dermatologists.)

Introduction: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease. Lesional skin of AD contains elevated levels of Th2, Th17, Th22 and Th1-citokines. With a growing movement toward use of targeted therapies, parallel to psoriasis, JAK inhibitors are an important focus of therapeutic research for AD. Methods: We review current evidence on the efficacy and safety of oral and topical JAK inhibitors for the treatment of AD. Results: Several JAK inhibitors are in phase II and III clinical trials as oral therapies for moderate-to-severe AD or as topical treatments for mild-to-moderate AD. Results thus far are encouraging, with the majority of the patients achieving the primary outcome of their trial as well as a favorable safety profile. Discussion: JAK inhibitors will most certainly be the first oral targeted option when topical therapy fails. With good oral bioavailability and lack of immunogenicity, they address some of the limitations of biologics. Yet to be defined is whether selective JAK 1 inhibitors or nonselective JAK inhibitors will provide the best equilibrium of efficacy versus side effects. Less clear is the position in the therapeutic ladder for topical JAK inhibitors; although, an unmeet need exists in the topical treatment of AD.

Introduction: Atopic dermatitis (AD) is a common chronic, pruritic inflammatory dermatosis. The inflammatory response is characterized by a T helper 2 (Th2) immune response phenotype., Evidence Acquisition: To assess current available data on dupilumab, the writers of this article did a comprehensive search in different databases, including Medline, EMBASE, SCOPUS, and clinical trial registries. All relevant articles identified were then manually reviewed. Information regarding dupilumab mechanism of action, pharmacokinetics, clinical efficacy, safety, and future trends was then summarized., Evidence Synthesis: Topical therapy is the main treatment in mild-to-moderate AD, but many cases of moderate-to-severe require systemic treatments. Dupilumab is the first biologic approved for the treatment of adults with moderate-to-severe AD. It inhibits IL-4 and IL-13 signaling pathways and reduces Th2 response. Clinical trials have demonstrated significantly improved clinical and patient-reported outcomes. The addition of application of topical corticosteroids results in a more significant improvement in signs and symptoms of AD than with use of dupilumab in monotherapy. The vast majority of patients improves under dupilumab, and almost 40% of patients achieve clear or nearly clear skin. In addition to its effectiveness, dupilumab also has a favorable safety profile. Frequent adverse events reported in the clinical trials were mostly mild-to-moderate and included nasopharyngitis, upper respiratory tract infection, injection site reactions, and conjunctivitis., Conclusions: In general, rates of adverse events occurred with similar frequency between the treatment and placebo groups. Conjunctivitis seems to be a dupilumab-specific side effect and so far has only been observed in atopic dermatitis patients (not in asthma or nasal polyposis). There were no major serious safety concerns identified in phase III clinical trials. Trials in the pediatric population are ongoing and are highly awaited.

With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.

Atopic dermatitis is a worldwide prevalent chronic inflammatory skin disease. Although primarily recognized as a disease of children, there is increasing evidence suggesting that it is more common in adults than previously thought. Both immune dysregulation and cutaneous barrier dysfunction are involved in the pathogenesis of the disease, although the exact mechanisms are still unclear. The concept of atopic dermatitis as a biphasic Th1-Th2 disease is changing, as recent evidence supports systemic activation of other multiple Th-cell subsets. Atopic dermatitis has been associated with an increasing number of comorbidities, possibly sharing some common pathological mechanisms. The atopic march is well known and represents the natural progression of atopic diseases in a considerable number of patients, usually starting with the development of atopic dermatitis followed by other atopic conditions, such as asthma and allergic rhinitis. Association of atopic dermatitis with cardiovascular disease, autoimmune diseases, as well as cutaneous and extracutaneous infections have been increasingly reported, although the link is not yet clear. Furthermore, the association between atopic dermatitis and neuropsychiatric conditions has also been widely studied, with an increased risk of mental health disorders strongly influenced by sleep disorders. Altogether, these associations contribute to the burden of atopic dermatitis, which increases the need for a more focused therapeutic approach that includes prevention or early diagnosis and treatment of comorbidities that may arise. This review explores the recent associations with atopic dermatitis and the possible underlying mechanisms involved, which supports the concept of atopic dermatitis as a systemic disease.

Atopic dermatitis (AD) is a common, chronic, inflammatory skin disorder with high physical and emotional burden. AD usually starts in early childhood and has a heterogeneous course. Emerging evidence suggests that IL-4 and IL-13 are key cytokines in the immunopathogenesis of AD. Dupilumab is a monoclonal antibody directed against IL-4 receptor α subunit, that blocks both IL-4 and IL-13 signaling. Data from Phase I-III studies revealed that dupilumab, administered as monotherapy or with topical corticosteroids, is effective and well tolerated in the treatment of adult patients with moderate-to-severe AD. A large proportion of patients receiving dupilumab had significant improvements in multiple efficacy indexes, including Eczema Area and Severity Index, Investigator's Global Assessment and SCORing Atopic Dermatitis scores. These results introduce a new era of targeted therapies in the management of AD., (Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)