Anti-IgE: lessons learned from effects on airway inflammation and asthma exacerbation

Omalizumab is an mAb that binds free IgE and ultimately reduces the density of IgE-loaded receptors on IgE effector cells. Because IgE effector cells, such as mast cells and basophils, are a source of proinflammatory chemokines, cytokines, and proteases, it is not surprising that omalizumab has anti-inflammatory effects, most notably large effects in reducing airway eosinophilia. What has been surprising is the nature of the clinical effects of omalizumab. Rates of exacerbation in omalizumab-treated patients are approximately half those in placebo-treated patients. This important clinical effect has occurred despite the fact that omalizumab does not improve nonspecific bronchial hyperesponsiveness and does not have large effects on airflow. The unsuspected dissociations among asthma outcomes uncovered during clinical trials of omalizumab remind us that mysteries remain for how inflammation, remodeling, and airway function are linked in asthma.