Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications
Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-1...
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2025-07-01
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| author | Renata Maria Văruț Dop Dalia Kristina Radivojevic Diana Maria Trasca George-Alin Stoica Niculescu Stefan Adrian Niculescu Elena Carmen Cristina Elena Singer |
| author_facet | Renata Maria Văruț Dop Dalia Kristina Radivojevic Diana Maria Trasca George-Alin Stoica Niculescu Stefan Adrian Niculescu Elena Carmen Cristina Elena Singer |
| author_sort | Renata Maria Văruț |
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| description | Asthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma. |
| format | Article |
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| institution | Kabale University |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-3b2a295eb6ea4e8e824d976e259ac6352025-08-20T03:32:17ZengMDPI AGPharmaceuticals1424-82472025-07-01187102110.3390/ph18071021Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical ApplicationsRenata Maria Văruț0Dop Dalia1Kristina Radivojevic2Diana Maria Trasca3George-Alin Stoica4Niculescu Stefan Adrian5Niculescu Elena Carmen6Cristina Elena Singer7Research Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaDepartment of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaResearch Methodology Department, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaDepartment of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaDepartment of Pediatric Surgery, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaDepartment of Orthopedics, University of Medicine and Pharmacy Craiova, 200349 Craiova, RomaniaDepartment of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaDepartment of Mother and Baby, University of Medicine and Pharmacy of Craiova, 200349 Craiova, RomaniaAsthma represents a heterogeneous disorder characterized by a dynamic balance between pro-inflammatory and anti-inflammatory forces, with allergic sensitization contributing substantially to airway hyperresponsiveness and remodeling. Central to its pathogenesis are cytokines such as IL-4, IL-5, IL-13, IL-17, and IL-33, which drive recruitment of eosinophils, neutrophils, and other effector cells, thereby precipitating episodic exacerbations in response to viral and environmental triggers. Conventional biomarkers, including blood and sputum eosinophil counts, IgE levels, and fractional exhaled nitric oxide, facilitate phenotypic classification and guide the emerging biologic era. Monoclonal antibodies targeting IgE (omalizumab) and IL-5 (mepolizumab, benralizumab, reslizumab, depemokimab) have demonstrated the ability to reduce exacerbation frequency and improve lung function, with newer agents such as depemokimab offering extended dosing intervals. Itepekimab, an anti-IL-33 antibody, effectively engages its target and mitigates tissue eosinophilia, while CM310-stapokibart, tralokinumab, and lebrikizumab inhibit IL-4/IL-13 signaling with variable efficacy depending on patient biomarkers. Comparative analyses of these biologics, encompassing affinity, dosing regimens, and trial outcomes, underscore the imperative of personalized therapy to optimize disease control in severe asthma.https://www.mdpi.com/1424-8247/18/7/1021airway inflammationcytokinestype 2 inflammationasthma exacerbations |
| spellingShingle | Renata Maria Văruț Dop Dalia Kristina Radivojevic Diana Maria Trasca George-Alin Stoica Niculescu Stefan Adrian Niculescu Elena Carmen Cristina Elena Singer Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications Pharmaceuticals airway inflammation cytokines type 2 inflammation asthma exacerbations |
| title | Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications |
| title_full | Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications |
| title_fullStr | Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications |
| title_full_unstemmed | Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications |
| title_short | Targeted Biologic Therapies in Severe Asthma: Mechanisms, Biomarkers, and Clinical Applications |
| title_sort | targeted biologic therapies in severe asthma mechanisms biomarkers and clinical applications |
| topic | airway inflammation cytokines type 2 inflammation asthma exacerbations |
| url | https://www.mdpi.com/1424-8247/18/7/1021 |
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