Promising Pipeline for CSU Options

Cleveland Clinic allergist Dr. David Lang joined Dr. Dawn Merritt and Dr. Brad P. Glick to discuss chronic spontaneous urticaria (CSU) at the 44th Annual Fall Clinical Dermatology Conference and noted that the future is very promising.

“Our recent understanding of chronic urticaria has improved dramatically, and we are now able to recognize four endotypes,” Dr. Lang said, adding that most of the important research in the category has been published within the past 2 years.

Dr. Lang noted the efficacy of omalizumab, which binds to circulating IgE, in studies. In type I autoallergic CSU, this can lead to rapid improvement, and in type IIb autoimmune CSU, omalizumab-induced reduction of free IgE can also lead to downregulation of FcεRI on skin mast cells, the target of mast cell-activating IgG autoantibodies, but improvement is more gradual.

Several emerging therapies under investigation for CSU were discussed, with Dr. Lang specifically highlighting remibrutinib and dupilumab. In the LIBERTY-CSU CUPID study, positive changes were seen in Itch Severity Score over 7 days (ISS7), Urticaria Activity Score summed over 7 days (UAS7), and Weekly Hives Severity Score (HSS7)  from baseline at Week 24; overall treatment-emergent adverse events reported in >5% of patients in any treatment group were comparable for placebo and dupilumab. In the REMIX-1 study, more than half of patients achieved UAS7≤6 with remibrutinib by Week 24.

Remibrutinib’s mechanism of action is activation of BTK, a cytoplasmic tyrosine kinase expressed in mast cells and basophils, leading to degranulation of mast cells and basophils and causing the release of histamine and other proinflammatory mediators.