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Mepolizumab and eosinophil-mediated disease.

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 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.
AuthorsG M Walsh
JournalCurrent medicinal chemistry (Curr Med Chem) Vol. 16 Issue 36 Pg. 4774-8 ( 2009) ISSN: 1875-533X [Electronic] United Arab Emirates
PMID19929788 (Publication Type: Journal Article, Review)
Chemical References
  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-5
  • mepolizumab
Topics
  • Anti-Asthmatic Agents (therapeutic use)
  • Antibodies, Monoclonal (therapeutic use)
  • Antibodies, Monoclonal, Humanized
  • Asthma (drug therapy)
  • Eosinophilia (drug therapy)
  • Eosinophils (drug effects, immunology)
  • Esophagitis (drug therapy)
  • Humans
  • Hypereosinophilic Syndrome (drug therapy)
  • Interleukin-5 (metabolism)

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