Many patients with severe asthma have elevated numbers of eosinophils (a subset of white blood cells) and raised serum concentrations of immunoglobulin E (IgE; antibodies). Elevated eosinophil counts together with IgE concentrations are associated with more frequent asthma attacks. Benralizumab is a drug that almost completely depletes eosinophils and significantly reduces asthma attacks for patients with severe, uncontrolled asthma and elevated blood eosinophil counts. The individual influence of eosinophils and IgE on benralizumab efficacy has been published. In this study, we further extend the analyses to evaluate the interrelationship of eosinophil counts and IgE concentrations with asthma attack frequency and benralizumab efficacy for patients with severe, uncontrolled asthma. We evaluated the association of blood eosinophil counts and IgE concentrations with asthma attack frequency for patients with severe asthma who received high-dosage inhaled corticosteroids plus additional controller medications but did not receive benralizumab in the benralizumab clinical trials. We observed that increased blood eosinophil counts were associated with greater asthma attack frequency, while serum IgE concentrations had no influence on asthma attack frequency. We also evaluated patients who received benralizumab and determined that benralizumab can reduce the occurrence of these attacks for patients with elevated blood eosinophil counts regardless of their serum IgE concentrations. Frequency of asthma attacks also decreased with benralizumab for patients with elevated serum IgE concentrations, but serum IgE concentrations did not influence benralizumab efficacy. Benralizumab is an efficacious treatment for patients with uncontrolled eosinophilic asthma, regardless of their IgE concentrations.