**4. Newly introduced anti-IgE therapies**

As a third-line therapy in patients with CSU, omalizumab is an effective and safe biological therapy option for both antihistamine-resistant CSU patients and physicians dealing with CSU [40]. However, there are nonetheless many patients who do not tolerate or benefit from existing and the other third-line therapies including omalizumab [41].

MEDI-4212, ligelizumab (QGE031), and mAbs targeting the extracellular segment (M1′) of membrane IgE: quilizumab is a new anti-IgE reagents that is currently undergoing phase II trial testings [42, 43].

#### **4.1. Ligelizumab (QGE031)**

Ligelizumab is a completely humanized IgG1 monoclonal antibody directed in opposition to human IgE that binds with excessive affinity to the Cε3 area of IgE. It also binds to Cε3 area of IgE with much more affinity than omalizumab [41]. Compared to omalizumab, ligelizumab suggests sixfold to ninefold more suppression of allergen-induced skin prick exams *in vivo*. It also affords more and longer suppression of free IgE and IgE on the surface of circulating basophils compared to omalizumab [44].

Current findings suggest that ligelizumab can be more potent than omalizumab within the treatment of CSU. The advent of an even stronger anti-IgE mAb-ligelizumab is developing; in addition, possibilities for anti-IgE therapy to improve the symptoms and life quality of patients with chronic urticaria [40, 41].

#### **4.2. Quilizumab**

Quilizumab is a humanized monoclonal antibody that targets the M1 prime of membraneexpressed IgE on IgE-switched B cells and plasmablasts. Quilizumab is in the medical development for the remedy of allergic diseases. By inflicting the depletion of IgE-switched B cells and plasmablasts, it reduces serum IgE [45].

A currently achieved multicenter, double-blind observe with 32 CSU patients showed that there was no significant difference between quilizumab and placebo group in terms of decreases in disease scores [46]. But its longer period use in CSU patients or its combination with omalizumab may enhance treatment effects and lead to sustained responses. This has to be revealed in future studies [41].

These findings suggest that quilizumab may be an effective treatment of CSU. Quilizumab and ligelizumab are still under investigation in CSU [41].
