Biologics for chronic spontaneous urticaria: toward a personalized treatment.

Chronic spontaneous urticaria (CSU) is characterized by the recurrent occurrence of short-lived wheals with or without angioedema for more than 6 weeks. Although its pathogenesis is not completely defined, several mechanisms seem involved, including autoimmunity and autoallergy with complement and coagulation activation. Various biologics are currently available or under investigation to counteract different CSU pathomechanisms. The recent literature dealing with biologics in the treatment of CSU was screened and analyzed; the different treatments were divided into anti-IgE and other than anti-IgE biologics. The latter were subdivided according to their target mechanisms. Biologic drugs exert their effects in a very precise and specific manner. A majority of patients (arguably those with type I disease) respond to anti-IgE treatment. Others, possibly with type IIa disease, show a slow response to anti-IgE drugs. Things are much more complicated in anti-IgE-refractory patients. Some respond well to nonspecific immune suppressors, such as corticosteroids and cyclosporin suggesting that an immune-mediated pathogenic mechanism, not involving the high-affinity IgE receptor, is probably active. Several ongoing studies are evaluating biologics and small molecules counteracting other pathomechanisms, including anti-receptor biologics, Bruton tyrosine kinase (BTK) inhibitors, mast cell targets, and specific cytokines.