New urticaria treatment options are currently being studied for patients with chronic spontaneous urticaria. Currently the only approved biologic medication approved for this condition is Xolair. Several medications are also being used off label and novel biologics are currently in development. Here we discuss them:
Dupilumab– In preclinical studies, dupilumab (Dupixent) blocked several functions of mast cells, the key drivers of chronic hives. A small study showed the benefit for 6 patients who failed Xolair. Dupixent is a key blocker of IL-4 and IL-13 which inhibits Th-2 disease.
Benralizumab, mepolizumab and reslizumab- IL-5 may contribute to the pathogenesis of chronic hives by directs effects on skin mast cells by promoting the recruitment of eosinophils and basophils to skin sites of wheal development. All 3 of these medications are licensed for asthma and have been successfully used to treat chronic hives and are being studied. Benralizumab is an anti-IL-5 receptor antibody and mepolizumab and reslizumab are anti IL-5 antibodies.
Secukinumab is an anti-IL-17 monoclonal antibody (Novartis) that showed a markedly reduced disease activity in patients with chronic hives who were refractory to other treatment options. IL-17 is associated with many autoimmune disorders and IL-17 has been elevated it patients with chronic urticaria.
Ligelizumab like Xolair is a humanized monoclonal antibody that binds IgE. It is different that that it has a higher affinity for IgE and a lower off rate. Phase 3 studies are ongoing.
GI-310 is anovel long acting IgE Trap-Fc fusion protein, binds circulating IgE. GI-301 exhibits higher and more durable binding to IgE than xolair and inhibits IgE driven human mast cells degranulation more potently. It is under development for chronic urticaria.
Tezepelumab is anti-TSLP human monoclonal antibody that prevents TSLP/TSLP receptor interaction. Mast cells express TSLP and induces mast cell development. It has been demonstrated for use in asthma and tezepelumab is being developed for chronic spontaneous urticaria.
Avdoralimab is a monoclonal antibody that blocks C5aR1. The C5a receptor is expressed by human skin mast cells and results in their activation and degranulation. Avdoralimab is currently being development for the treatment of Covid-19 and assessed for its effects in hives.
Lirentelimab is a humanized IgG1 anti-Siglec-8 monoclonal antibody that inhibits mast cell activation and depletes eosinophils.
LY3454738 is a humanized mAb that binds to and agonizes CD200R which would inhibit mast cell activation and degranulation as well as cytokine production and release.
CDX-0159 is a mAb that binds the extracellular dimerization domain of Kit, inhibits activation by KIT. KIT (CD117) is the receptor that is the major driver of Mast Cell differentiation, activation, migration, proliferation and survival.