New treatments for chronic urticaria.

Chronic urticaria (CU) is a common, heterogeneous and debilitating disease. Antihistamines and omalizumab are the mainstay therapies of CU. Additional treatment options are needed. Here, we review the off and beyond label use of licensed drugs, novel treatments that are currently under development, and promising new targets.and Study Selection: We performed a thorough search of the recent literature on reports of the successful use of treatments in CU and promising targets for the development of novel treatment options. Also, we searched clinicaltrials.gov for recent and ongoing randomized controlled trials in CU.Omalizumab, the treatment of choice in patients with antihistamine-resistant chronic spontaneous urticaria (CSU), should be explored for the use in chronic inducible urticaria, in children <12 years old with CSU, and at higher doses. The off label use of dupilumab, reslizumab, mepolizumab and benralizumab can be effective in CU. Ligelizumab and UB-221, two novel anti-IgE monoclonal antibodies are in clinical trials for CU. Other promising drugs that are currently under development for CU are a CRTh2 antagonist, a monoclonal antibody to Siglec-8 (AK002), Bruton's tyrosine kinase inhibitors (Fenebrutinib and Lou064), a Syk inhibitor and dupilumab. Promising targets of future therapies include the Mas-related G-protein coupled receptor X2, the H4 receptor, C5a and its receptor, inhibitory mast cell receptors other than Siglec-8, Interleukin-33/Interleukin-25/TSLP, and SCF.Novel and better treatments for CU are very much needed. Some are in clinical trials already, and additional ones should be developed, making use of the many promising targets recently identified and characterized.