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Atopic dermatitis: an expanding therapeutic pipeline for a complex disease.
Literature Information
| DOI | 10.1038/s41573-021-00266-6 |
|---|---|
| PMID | 34417579 |
| Journal | Nature reviews. Drug discovery |
| Impact Factor | 101.8 |
| JCR Quartile | Q1 |
| Publication Year | 2022 |
| Times Cited | 203 |
| Keywords | Atopic Dermatitis, Therapeutic Strategies, Precision Medicine |
| Literature Type | Journal Article, Review |
| ISSN | 1474-1776 |
| Pages | 21-40 |
| Issue | 21(1) |
| Authors | Thomas Bieber |
TL;DR
This review examines the advancements in therapeutic strategies for atopic dermatitis (AD), a challenging chronic inflammatory skin condition, highlighting recent discoveries of novel drug candidates and targets, including approved agents like dupilumab and emerging therapies. The findings underscore the potential for a precision medicine approach to improve prevention and long-term management of AD, enhancing treatment efficacy for diverse patient phenotypes.
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Atopic Dermatitis · Therapeutic Strategies · Precision Medicine
Abstract
Atopic dermatitis (AD) is a common chronic inflammatory skin disease with a complex pathophysiology that underlies a wide spectrum of clinical phenotypes. AD remains challenging to treat owing to the limited response to available therapies. However, recent advances in understanding of disease mechanisms have led to the discovery of novel potential therapeutic targets and drug candidates. In addition to regulatory approval for the IL-4Ra inhibitor dupilumab, the anti-IL-13 inhibitor tralokinumab and the JAK1/2 inhibitor baricitinib in Europe, there are now more than 70 new compounds in development. This Review assesses the various strategies and novel agents currently being investigated for AD and highlights the potential for a precision medicine approach to enable prevention and more effective long-term control of this complex disease.
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Primary Questions Addressed
- What are the specific mechanisms of action for the novel therapeutic agents being developed for atopic dermatitis?
- How do the newly approved therapies for atopic dermatitis compare in terms of efficacy and safety profiles?
- What role does precision medicine play in the treatment of atopic dermatitis, and how might it change future therapeutic strategies?
- Are there any recent clinical trial results that highlight the effectiveness of the new compounds in development for atopic dermatitis?
- How does the understanding of the pathophysiology of atopic dermatitis influence the selection of treatment options for patients?
Key Findings
Research Background and Objectives
Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder characterized by a complex pathophysiology, which results in diverse clinical manifestations. The disease often begins in childhood, impacting the quality of life and imposing significant socio-economic burdens. Current treatment options are limited, leading to a pressing need for new therapeutic strategies. This review evaluates emerging therapeutic agents and approaches in AD management, aiming to highlight the potential for precision medicine in the treatment of this multifaceted disease.
Main Methods/Materials/Experimental Design
The review systematically analyzes over 70 compounds currently under investigation for AD, focusing on their mechanisms of action and therapeutic potential. The research employs a multidimensional model of AD, encompassing factors such as genetic predisposition, immune response, environmental triggers, and the skin microbiome. The analysis includes both preclinical and clinical trial data to assess the efficacy and safety of novel agents.
Key Results and Findings
Therapeutic Agents:
- Biologics targeting specific cytokines (e.g., IL-4, IL-13) such as dupilumab and tralokinumab have shown efficacy in moderate to severe AD.
- JAK inhibitors (e.g., baricitinib, ruxolitinib) demonstrate rapid relief of symptoms and are in advanced clinical trials.
- Novel strategies involving microbiome modulation and barrier restoration are emerging, with promising early results from compounds like FB-401 and tapinarof.
Comorbidities: AD is associated with various comorbidities, including allergic asthma and psychiatric disorders, complicating its management and highlighting the need for integrated treatment approaches.
Clinical Trial Outcomes: Many trials indicate significant improvements in disease severity and patient-reported outcomes, although variability in response rates underscores the necessity for tailored treatment plans.
Main Conclusions/Significance/Innovation
The expanding therapeutic pipeline for AD signifies a shift towards more targeted and effective treatment options, moving beyond traditional "one-size-fits-all" strategies. The integration of precision medicine, focusing on individual patient profiles, genetic backgrounds, and specific immune pathways, is expected to enhance long-term management of AD. This approach could lead to better disease control and quality of life for patients.
Research Limitations and Future Directions
Despite promising developments, several limitations persist:
- The heterogeneity of AD makes it challenging to predict treatment responses across different patient populations.
- The long-term safety profiles of new therapies, particularly biologics and JAK inhibitors, require further investigation.
- Future research should focus on identifying biomarkers that can predict therapeutic responses and stratifying patients based on phenotypic and genotypic characteristics.
In conclusion, ongoing research and clinical trials are essential to fully realize the potential of novel therapies and precision medicine in the management of atopic dermatitis, ultimately aiming to improve patient outcomes and reduce the burden of this complex disease.
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Literatures Citing This Work
- [Inappropriate systemic therapy in severe atopic dermatitis-severe long-term damage]. - F Abeck;N Booken;S Schneider - Dermatologie (Heidelberg, Germany) (2022)
- The link between atopic dermatitis and asthma- immunological imbalance and beyond. - Martina Yaneva;Razvigor Darlenski - Asthma research and practice (2021)
- Flare management in atopic dermatitis: from definition to treatment. - Giampiero Girolomoni;Valentina Maria Busà - Therapeutic advances in chronic disease (2022)
- The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders. - João P Luís;Carlos J V Simões;Rui M M Brito - International journal of molecular sciences (2022)
- Anti-atopic dermatitis effects of Parasenecio auriculatus via simultaneous inhibition of multiple inflammatory pathways. - Yujin Kwon;Su-Yeon Cho;Jaeyoung Kwon;Min Hwang;Hoseong Hwang;Yoon Jin Kang;Hyeon-Seong Lee;Jiyoon Kim;Won Kyu Kim - BMB reports (2022)
- Bruton's tyrosine kinase inhibition-An emerging therapeutic strategy in immune-mediated dermatological conditions. - Pedro Mendes-Bastos;Ana Brasileiro;Pavel Kolkhir;Stefan Frischbutter;Jörg Scheffel;Sherezade Moñino-Romero;Marcus Maurer - Allergy (2022)
- Atopic Dermatitis Pathogenesis: Lessons From Immunology. - Luis F Santamaria-Babí - Dermatology practical & conceptual (2022)
- 1-Iodohexadecane Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice: Possible Involvements of the Skin Barrier and Mast Cell SNARE Proteins. - Do Yoon Kim;Kyung-Jong Won;Dae Il Hwang;Nan Young Kim;Bokyung Kim;Hwan Myung Lee - Molecules (Basel, Switzerland) (2022)
- Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets. - Luca Fania;Gaia Moretta;Flaminia Antonelli;Enrico Scala;Damiano Abeni;Cristina Albanesi;Stefania Madonna - International journal of molecular sciences (2022)
- Immunopathology and Immunotherapy of Inflammatory Skin Diseases. - Ahreum Song;Sang Eun Lee;Jong Hoon Kim - Immune network (2022)
... (193 more literatures)
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