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

Urticaria treatment has evolved a lot during the past decade. Current guidelines for the treatment of chronic spontaneous urticaria recommend the use of omalizumab, an IgE-targeted biologic. IgE has high-affinity to the receptor FcεRI, and degranulate skin mast cells, which are responsible for the development of signs and symptoms of urticaria, itchy wheals and angioedema. This study aims to review the existing understanding of the pathogenesis of chronic urticaria and its autoimmune endotypes.

Omalizumab is the only licensed biologic for use in chronic urticaria from 12 years old age. It is recommended as the third step of the therapy in patients who have failed standard or high-dose second-generation antihistamines and is generally well tolerated. Omalizumab has multiple potential mechanisms of action in chronic urticaria, with effects on mast cells and basophils, reducing mediators’ release and decreasing FcεRI expression. It has been approved for chronic urticaria at doses of 150 or 300 mg every 4 weeks. Poor responders may benefit from shortening the dosing interval to every 2 or 3 weeks or by adjunctive therapy with cyclosporine 3 mg/kg/day for 4 months each.

Some other biologic drugs used as off-label in chronic urticaria include dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab. New biologics under development aim to reduce mast cell activation by blocking activating pathways or engaging inhibitory receptors or mast cell numbers. These include ligelizumab and GI-301, avdoralimab, tezepelumab, lirentelimab, LY3454738, and CDX-0159 at different stages of development.