New treatments for chronic urticaria

Objective: 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.

Data sources: MEDLINE was searched for recent reports of the successful use of treatments in CU and promising targets for the development of novel treatment options. We also searched ClinicalTrials.gov for recent and ongoing randomized clinical trials in CU.

Study selections: Relevant articles were selected and reviewed.

Results: Omalizumab, the treatment of choice in patients with antihistamine-resistant chronic spontaneous urticaria (CSU), should be explored for use in chronic inducible urticaria in children younger than 12 years 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, 2 novel anti-IgE monoclonal Antibodies, are in clinical trials for CU. Other promising drugs that are currently under development for CU are a chemoattractant receptor-homologous molecule expressed on T_H2 cell antagonist, a monoclonal antibody to Siglec-8 (AK002), Bruton tyrosine kinase inhibitors (fenebrutinib and Lou064), a spleen tyrosine kinase inhibitor, and dupilumab. Promising targets of future therapies include the Mas-related G-protein-coupled receptor X2; the histamine₄ receptor; C5a and its receptor; inhibitory mast cell receptors other than Siglec-8; interleukin 33, interleukin 25, and thymic stromal lymphopoietin, and stem cell factor.

Conclusion: Novel and better treatments for CU are very much needed. Some agents are in clinical trials already (eg, ligelizumab), and additional ones should be developed, making use of the many promising targets recently identified and characterized.