Omalizumab-resistant IgE variants and methods of using them in combination with omalizumab for treatment of IgE-mediated disorders, including allergic diseases, inflammation, and asthma are disclosed. In particular, the invention relates to omalizumab-resistant IgE variants comprising mutations that interfere with omalizumab binding. These IgE variants can be used in combination therapy with omalizumab to effectively exchange the IgE repertoire on basophils by allowing the replacement of harmful allergic IgE species, depleted by omalizumab, with benign IgE species.
