The current only approved treatment for hives are antihistamines and Xolair (omalizumab). Omalizumab is approved for the treatment of chronic hives for those 12 years and older (it is approved for 6 years and older in asthma). New treatment for hives are on the horizon.
Ligelizumab is a next generation high affinity monoclonal anti-IgE under development for the treatment of chronic spontaneous urticaria. In comparison to omalizumab, ligelizumab has a 40 to 50 times greater affinitiy for IgE. Patients treated with it demonstrated a rapid onset of drug effect, dose-dependent efficacy, and superiority over Xolair as more than 50% of patients taking the highest dose were complete responders; more than double for Xolair. In addition patients treated with ligelizumab had suppression of symptoms for up to 8 weeks comparred with the 4 week duration of Xolair. (Although in previous blog posts we have written about Xolair lasting up to 12 weeks in some patients).
Dupilumab (Dupixent) is a monoclonal antibody that inhibits IL-4 and IL-13 signaling by blocking the IL-4 alphay receptor, it is approved for eczema, asthma and nasal polyps. Smaller studies showed a favorable response in patients with chronic hives who failed high dose antihistamines and Xolair.
Nucala, Fasenra and Cinqair affect the production of eosinophils and their products such as major basic protein, they have been reported to contribute to the pathogenesis of chronic hives. Mast cells may recruit eosinophils through the release of IL-5. These meds are currently under investigation.
Prostaglandin D2 is a product of activated mast cells and induces eosinophils and basophils. AZD1981 is an oral selective and reversible CRTh2 antagonist (chemoattractant receptor homologous protein). It has been shown to reduce itch and blood eosinophils in patients in 18 to 65 years old in patients refractory to antihistamines.
Fenebrutinib (GDC-0853) is a highly selective, reversible oral BTK inhibitor undergoing clinical investigation for use in chronic hives. BTK is a cytoplasmic tyrosine kinase involved in cell signaling. Ibrutinib is a nonspecific oral Btk inhibitor showing an effect in inhibition of IgE-mediated activation of mast cells and basophils. LOU-064 is another Btk inhibtor currently under evaluation. Other targets in different stages of development inhibit JAK1/2 kinases, TNF-alpha, IL-1, MRGPRX2, histamine-4-receptor, C5a and C5aR, IL-33, IL-25, thymic stromal lymphopoietin and stem cell factor.
These additional therapies may address the needs of more difficult to manage and often vulnerable patients with chronic hives. The future is bright for developing safe and effective therapies targeting novel pathways which should lead to a better understanding of chronic hives and improving clinical outcomes.