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IgE plays a pivotal role in allergic asthma especially in the acute response to antigen and in the propagation of airway inflammation. Therefore, it has become apparent that targeting this antibody and blocking its function may lead to significant clinical effects in some patients with the disease. In this review, we describe the role of IgE in asthma and provide an update on the therapeutic implications of targeting this mediator in patients with severe allergic disease. We also outline future needs of research in this area.Several randomized clinical trials as well as observational real-world studies have confirmed the long-term efficacy of omalizumab in improving clinical outcomes when added to guideline-recommended maintenance of asthma medications (inhaled corticosteroids and long-acting β2-agonists) in patients with moderate-to-severe asthma. Recent pooled data from randomized clinical trials and from a large prospective cohort study provide reassurance about the long-term safety of omalizumab. Future research should explore the long-term effects of omalizumab on the natural history of the disease and identify more accurate predictors of response to this treatment.The anti-inflammatory effects of omalizumab at different sites of allergic inflammation and its clinical benefits in patients with allergic asthma emphasize the fundamental importance of IgE in allergic inflammation.