Biologics for the Use in Chronic Spontaneous Urticaria: When and Which

Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease. The rationale for this is supported by the key role of IgE and its high-affinity receptor, FceRI, in the degranulation of skin mast cells that drives the development of the signs and symptoms of CSU, itchy wheals, and angioedema. Here, we review the current understanding of the pathogenesis of CSU and its autoimmune endotypes. We describe the mechanisms of action of omalizumab, the only biologic currently approved for CSU, its efficacy and ways to improve it, biomarkers for treatment response, and strategies for its discontinuation. We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. Finally, we discuss targets for novel biologics and where we stand with their clinical development. These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acidebinding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future. (C) 2020 American Academy of Allergy, Asthma & Immunology

Automated summary

The guidelines recommend the use of omalizumab in antihistamine-refractory CSU, highlighting the key role of IgE and FcεRI in the pathogenesis. The review covers mechanisms of action, biomarkers, and strategies for improving treatment efficacy, as well as exploring off-label use of other biologics. Future directions include novel biologics targeting various pathways in CSU treatment.