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.