The future of targeted therapy in chronic spontaneous urticaria

Chronic urticaria can be divided into two subsets: chronic spontaneous urticaria (CSU) with skin lesions occurring without a specific trigger and chronic inducible urticaria (CIndU) which has an identified specific stimulus. The annual prevalence of CU is 0.5% to 2.3% globally. CSU is a self-limited disorder in most cases, with an average duration of 2 to 5 years, but symptoms persist beyond five years in up to 30% of patients. The first line of treatment is a daily non-sedating, second-generation H1- antihistamines. CSU guidelines recommend using oral non-sedating antihistamines up to 4-fold in patients with CSU unresponsive to standard doses as the next step in treatment. A meta-analysis found that the rate of response in patients with CSU who responded to up-dosing was 63.2%. Therefore, approximately 40% of patients continue to have persistent hives and itching requiring treatment with the biologic omalizumab based on evidence from randomized controlled trials. Although omalizumab has been shown to markedly improve symptoms of CSU, omalizumab is not effective in all patients and has not been shown to induce long-term disease remission. Thus, there is an unmet need for more effective treatments that can lead to cure or long-term remission. In this review, we will provide an overview of new treatment targets and biologics that are under investigation for the treatment of CSU.