Abstract
Eosinophils are major pro-inflammatory cells that make a major contribution to diseases that affect the upper and lower airways, skin and gastrointestinal tract. Interleukin (IL)-5 is central to their maturation and release from the bone marrow together with their subsequent accumulation and activation in the tissues. Mepolizumab is a humanized monoclonal antibody (mAb) with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases. Several clinical trials with mepolizumab reported that treatment of patients with mild to severe asthma resulted in a substantial reduction in blood and sputum eosinophil numbers. However, clinical outcomes were disappointing as there were no significant effects on airway hyper-reactivity or the late asthmatic reaction to inhaled allergen challenge. More recently two studies, one in patients with refractory eosinophilic asthma with a history of recurrent severe exacerbations and the other in patients with persistent sputum eosinophilia and symptoms despite systemic treatment with prednisone treatment, reported that monthly intravenous mepolizumab reduced sputum/blood eosinophilia, asthma exacerbations together with improvments in quality of life. Mepolizumab also appears to be an effective therapy for hypereosinophilic syndrome while other trials have shown efficacy of mepolizumab therapy in eosinophilic esophagitis. This review will consider the current status of the clinical development of mepolizumab for diseases with a significant eosinophilic component to their pathology.
Keywords: Mepolizumab, IL-5, Eosinophils, Asthma, Eosinophilic esophagitis, Hypereosinophilic syndrome
Current Medicinal Chemistry
Title: Mepolizumab and Eosinophil-Mediated Disease
Volume: 16 Issue: 36
Author(s): G. M. Walsh
Affiliation:
Keywords: Mepolizumab, IL-5, Eosinophils, Asthma, Eosinophilic esophagitis, Hypereosinophilic syndrome
Abstract: Eosinophils are major pro-inflammatory cells that make a major contribution to diseases that affect the upper and lower airways, skin and gastrointestinal tract. Interleukin (IL)-5 is central to their maturation and release from the bone marrow together with their subsequent accumulation and activation in the tissues. Mepolizumab is a humanized monoclonal antibody (mAb) with potent IL-5 neutralizing effects that represents a potential treatment for eosinophilic diseases. Several clinical trials with mepolizumab reported that treatment of patients with mild to severe asthma resulted in a substantial reduction in blood and sputum eosinophil numbers. However, clinical outcomes were disappointing as there were no significant effects on airway hyper-reactivity or the late asthmatic reaction to inhaled allergen challenge. More recently two studies, one in patients with refractory eosinophilic asthma with a history of recurrent severe exacerbations and the other in patients with persistent sputum eosinophilia and symptoms despite systemic treatment with prednisone treatment, reported that monthly intravenous mepolizumab reduced sputum/blood eosinophilia, asthma exacerbations together with improvments in quality of life. Mepolizumab also appears to be an effective therapy for hypereosinophilic syndrome while other trials have shown efficacy of mepolizumab therapy in eosinophilic esophagitis. This review will consider the current status of the clinical development of mepolizumab for diseases with a significant eosinophilic component to their pathology.
Export Options
About this article
Cite this article as:
Walsh M. G., Mepolizumab and Eosinophil-Mediated Disease, Current Medicinal Chemistry 2009; 16 (36) . https://dx.doi.org/10.2174/092986709789909639
DOI https://dx.doi.org/10.2174/092986709789909639 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Structure-Function Relationships and Clinical Applications of L-Asparaginases
Current Medicinal Chemistry High-dimensional Causal Mediation Analysis with a Large Number of Mediators Clumping at Zero to Assess the Contribution of the Microbiome to the Risk of Bacterial Pathogen Colonization in Older Adults
Current Bioinformatics Radiation-Induced Pulmonary Epithelial-Mesenchymal Transition: A Review on Targeting Molecular Pathways and Mediators
Current Drug Targets Meet The Guest Editor
Combinatorial Chemistry & High Throughput Screening The Interplay between the Gut Immune System and Microbiota in Health and Disease: Nutraceutical Intervention for Restoring Intestinal Homeostasis
Current Pharmaceutical Design Measurement of Antioxidant Activity and Antioxidant Compounds under Versatile Extraction Conditions: I. The Immuno-Biochemical Antioxidant Properties of Sweet Cherry (Prunus avium) Extracts
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry EDITORIAL (Thematic Issue): Vitamin D in Allergy and Chronic Airway Inflammation
Mini-Reviews in Medicinal Chemistry New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is)
Current Medicinal Chemistry Efficacy and Safety of H1-Antihistamines: An Update
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Biocatalysis in the Pharmaceutical Industry. A Greener Future
Current Green Chemistry Flavonoids and Related Compounds in Parasitic Disease Control
Mini-Reviews in Medicinal Chemistry New Computational Tool Based on Machine-learning Algorithms for the Identification of Rhinovirus Infection-Related Genes
Combinatorial Chemistry & High Throughput Screening α7 nAChR in Airway Respiratory Epithelial Cells
Current Drug Targets Design and Synthesis of Carbohydrate Derivatives for Antagonistic Activity at Muscarinic Receptor
Letters in Drug Design & Discovery A<sub>2A</sub> Adenosine Receptor Antagonists in Neurodegenerative Diseases
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Proteomics Matrix Metalloproteinases in Respiratory Diseases: From Pathogenesis to Potential Clinical Implications
Current Medicinal Chemistry Mast Cells and Basophils: Trojan Horses of Conventional Lin- Stem/Progenitor Cell Isolates
Current Pharmaceutical Design The Multidisciplinary Issue of Obesity: Epidemiological Studies, Company Strategies and Policy Actions: A Systematic and Methodological Review of the Research Approaches
Recent Patents on Food, Nutrition & Agriculture The Role of microRNA-126 in Vascular Homeostasis
Current Vascular Pharmacology