Mepolizumab treatment for asthma

Abstract

Introduction: Five percent of asthmatics have severe symptoms despite high doses of inhaled (ICS) or additional oral corticosteroids (OCS): these patients have high morbidity, risk for asthma death, and account for half of asthma healthcare spending. A subgroup (20 – 40%) of these has persistent airway eosinophilia and frequent exacerbations. Mepolizumab is a humanized monoclonal antibody that blocks binding of the key cytokine implicated specifically in eosinophil maturation and survival, interleukin-5, to its receptor.

Areas covered: Pharmacology, Phase I/IIa and Phase II/III studies of mepolizumab for asthma. Mepolizumab depleted blood and sputum eosinophils and partially reduced airway and bone marrow eosinophils. It also reduced airway remodeling. In unselected patients with moderate/severe asthma there was no clinically significant effect on lung function, but a trend to reduced exacerbation rates. When patients were selected for persistent sputum eosinophilia despite high-dose ICS/OCS, and frequent exacerbations, mepolizumab reduced exacerbations by 50%.

Expert opinion: Mepolizumab can reduce exacerbation rates in the severe asthma cohort who have eosinophilic airway inflammation despite corticosteroid treatment. This may be 30% of severe asthmatics and represents a new and important treatment option. Further studies need to confirm efficacy and indications for asthma (and other eosinophilic airway disease), and to examine clinical consequences of reducing remodeling.

Keywords::

• asthma
• exacerbation
• interleukin-5
• mepolizumab

Acknowledgment

The author thanks Professor I Pavord for discussion about mepolizumab.

Notes