Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs

Allergy, Год журнала: 2024, Номер 79(6), С. 1501 - 1515

Опубликована: Янв. 8, 2024

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high burden. In Europe, six new systemic therapies for AD have been approved: biologics dupilumab (anti-interleukin-4 receptor (IL-4R) α in 2017), tralokinumab (anti-IL-13 2021), lebrikizumab 2023), oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib 2020 EU) or JAK1 (upadacitinib 2021 abrocitinib 2022). Herein, we give an update on approvals, long-term safety, efficacy. Upadacitinib highest short-term efficacy among approved therapies. responders, catch up regarding incremental clinical benefit within continuous use. Recently, European Medicines Agency has released recommendations use of JAKi patients at risk (cardiovascular thromboembolic diseases, malignancies, (former) smoking, age ≥65 years). Furthermore, overview emerging currently Phase III trials. Among topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan-JAKi), asivatrep (anti-transient potential vanilloid), phosphodiesterase-4-inhibitors (roflumilast, difamilast) are discussed. current data cord-blood-derived mesenchymal stem cells, CM310 (anti IL-4Rα), nemolizumab (anti-IL-31RA), anti-OX40/OX40L-antibodies, neurokinin-receptor-1-antagonists, difelikefalin (κ-opioid-R) reported.

Язык: Английский

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Neuroimmune interplay during type 2 inflammation: Symptoms, mechanisms, and therapeutic targets in atopic diseases

Journal of Allergy and Clinical Immunology, Год журнала: 2023, Номер 153(4), С. 879 - 893

Опубликована: Авг. 25, 2023

Type 2 inflammation is characterized by overexpression and heightened activity of type cytokines, mediators, cells that drive neuroimmune activation sensitization to previously subthreshold stimuli. The consequences altered differ tissue disease; they include skin inflammation, pruritogens, itch amplification in atopic dermatitis prurigo nodularis; airway and/or hyperresponsiveness, loss expiratory volume, airflow obstruction increased mucus production asthma; sense smell chronic rhinosinusitis with nasal polyps; dysphagia eosinophilic esophagitis. We describe the interactions underlie various sensory autonomic pathologies inflammatory diseases present recent advances targeted treatment approaches reduce its associated symptoms these diseases. 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Pathophysiology esophagitis.Gastroenterology. 154: 333-345Abstract 71Akiho Ihara Motomura Nakamura Cytokine-induced alterations disorders.World Gastrointest Pathophysiol. 2011; 2: 72-81Crossref 72Hu Liu al.Increased acid responsiveness guinea pig esophagitis.Am Physiol Liver 307: G149-G157Crossref (21) 73Zhang Shoda Arva N.C. Chehade Collins M.H. al.Mast cell-pain connection esophagitis.Allergy. 77: 1895-1899Crossref (8) Scholar).Table INeuroimmune affecting AD, PN, CRSwNP, EoEConditionSymptomsNeuroimmune interactionsType profileADPruritus•Colocalization cells7Kulka Scholar,8Liang Scholar•Type OSM promote pruritogen sensitization9Sonkoly Scholar•Neuropeptide proinflammatory basophils)7Kulka Scholar,10Tominaga Scholar•Scratching causes alarmins IL-33), which can act neurons9Sonkoly Scholar,11Garcovich Scholar,14Liu Scholar•Some express receptors IL-13, IL-31, TRPA1, TRPV118Oetjen Scholar,19Cevikbas Scholar•Reducing reduces itch20Blauvelt

Язык: Английский

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Skin biomarkers predict the development of food allergy in early life

Journal of Allergy and Clinical Immunology, Год журнала: 2024, Номер 153(5), С. 1456 - 1463.e4

Опубликована: Март 3, 2024

Язык: Английский

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Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis

Pharmaceutics, Год журнала: 2023, Номер 15(2), С. 577 - 577

Опубликована: Фев. 8, 2023

Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also recovery of damaged skin barrier. The current review focuses on interleukin 31 (IL-31) pathway AD offers an overview clinical studies monoclonal antibodies blocking this cascade. Pruritus, key symptom AD, substantial participation IL-31 complex activation relevant signaling pathways. Epidermal keratinocytes, cells, cutaneous peripheral nerves express interleukin-31 receptor α-chain (IL-31RA), upregulated by Staphylococcus aureus toxins or Th2 cytokines involved in AD. Nemolizumab is humanized antibody that antagonizes IL-31RA, inhibiting cascade therefore contributing reducing pruritus inflammation recovering barrier patients. Phases 2 3 trials nemolizumab show suitable safety profile, fast, efficient, sustained reduction severity scores, especially when associated topical treatment. Deciphering full interplay may expand potential as targeted therapy for other pruritic conditions.

Язык: Английский

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Navigating the evolving landscape of atopic dermatitis: Challenges and future opportunities: The 4th Davos declaration

Allergy, Год журнала: 2024, Номер 79(10), С. 2605 - 2624

Опубликована: Авг. 4, 2024

Abstract The 4th Davos Declaration was developed during the Global Allergy Forum in which aimed to elevate care of patients with atopic dermatitis (AD) by uniting experts and stakeholders. forum addressed high prevalence AD, a strategic focus on advancing research, treatment, management meet evolving challenges field. This multidisciplinary brought together top leaders from clinical practice, policy, patient advocacy discuss critical aspects including neuroimmunology, environmental factors, comorbidities, breakthroughs prevention, diagnosis, treatment. discussions were geared towards fostering collaborative approach integrate these advancements into practical, patient‐centric care. underlined mounting burden attributing it significant lifestyle changes. It acknowledged progress understanding AD developing targeted therapies but recognized gap translating innovations practice. Emphasis placed need for enhanced awareness, education, stakeholder engagement address this effectively consider factors comprehensive disease strategy. marks milestone journey improve people AD. By promoting holistic that combines application, sets roadmap stakeholders collaborate outcomes reflecting commitment adapt respond dynamic changing world.

Язык: Английский

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Dupilumab Inhibits Vascular Leakage of Blood Proteins Into Atopic Dermatitis Skin

The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2023, Номер 11(5), С. 1421 - 1428

Опубликована: Март 22, 2023

Язык: Английский

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Integrating multi‐omics approaches in deciphering atopic dermatitis pathogenesis and future therapeutic directions

Allergy, Год журнала: 2024, Номер 79(9), С. 2366 - 2379

Опубликована: Июнь 4, 2024

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in spectrum of clinical subtypes. The application genomics has elucidated the role genetic variations predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on molecular underpinnings Proteomics explores involvement proteins AD pathophysiology, while epigenomics examines impact environmental factors expression. Lipidomics, which investigates lipid profiles, enhances our understanding barrier functionalities their perturbations This review synthesizes insights from these omics approaches, highlighting collective importance unraveling intricate pathogenesis culminates by projecting future trajectories research, particularly promise multi-omics forging personalized medicine novel therapeutic interventions. Such an integrated strategy is poised transform comprehension management, steering towards more precise efficacious treatment modalities.

Язык: Английский

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Real-World Efficacy and Safety of Dupilumab Use in Japanese Adult Patients with Atopic Dermatitis: A Single-Center, Retrospective, 104-Week, Observational Study

Diseases, Год журнала: 2025, Номер 13(2), С. 44 - 44

Опубликована: Фев. 3, 2025

Background/Objectives: Dupilumab is an interlekin-4 receptor antibody that exerts its efficacy by inhibiting the signaling pathway of interleukin-4/interleukin-13, and it currently used clinically as a highly potent therapeutic for atopic dermatitis. However, there have been few reports on effect dupilumab using long-term real-world data. To accumulate further data through use dupilumab, we performed retrospective study courses patients with dermatitis who were treated at least 104 weeks in our university hospital. Methods: We examined treatment 30 adult patients. Results: Subjective (e.g., itch visual analog scale Dermatology Life Quality Index) objective Eczema Area Severity indices some biomarkers showed improvements over time treatment, even cases poor early response to treatment. As anatomical regions, although head neck region was weak stages, improved time, weeks, comparable other regions. Conclusions: Therefore, demonstrated advantages prolonged administration

Язык: Английский

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Subcutaneous Injection and Brush Application of Ovalbumin–Aluminum Salt Solution Induces Dermatitis-like Changes in Mice

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(5), С. 1701 - 1701

Опубликована: Март 3, 2025

Background: Intraperitoneal sensitization combined with topical and/or epicutaneous treatment using an ovalbumin (OVA)–aluminum salt solution (OVA-AL) represents a model for inducing atopic dermatitis (AD). However, the combination of subcutaneous and cutaneous application OVA-AL via brush has not been explored as method AD. Methods: Adult mice were subcutaneously injected following on days 0, 7, 14 treated to dorsal skin fortnightly until 35 49. Concomitant alloknesis changes assessed. Mice Balb/c ICR-CD1 strains day 35, only strain continuing Control animals received saline. At 49 days, was harvested processed histological analysis. Results: developed dry skin, no scratching or alloknesis. Histological examination revealed increase in mast cells collagen deposition. Conclusions: Dermatitis-like symptoms observed this administration method.

Язык: Английский

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Association between organophosphate pesticide exposure and atopic dermatitis: a cross-sectional study based on NHANES 1999–2007

Frontiers in Public Health, Год журнала: 2025, Номер 13

Опубликована: Март 6, 2025

Organophosphate pesticides (OPPs) are widely used environmental chemicals with potential health impacts, but their relationship atopic dermatitis (AD) remains unclear. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2007, we investigated associations between urinary OPP metabolites AD in 4,258 adults. Six dialkyl phosphate (DAP) were measured, weighted quantile sum (WQS) regression was to assess mixture effects. Both DMP (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.05-1.31) DMDTP (OR 2.23, 95%CI: 1.08-4.60) showed significant positive fully adjusted models. WQS revealed mixed exposure 1.25, 1.04-1.50), contributing most (45.8%) effect. Stratified analyses indicated stronger males, younger adults (<60 years), smokers. Our findings suggest that exposure, particularly DMP, may be associated increased risk These results provide new insights into factors for AD.

Язык: Английский

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