Chronic spontaneous urticaria (CSU) is defined by recurring hives, swelling, or both, and lasting 6 weeks or more, without identifiable triggers such as allergies or external stimuli. Dawn Merritt, DO, Mark Lebwohl, MD, and Marc Serota, MD, examined the challenges of second-line antihistamine treatments, explored new therapies, and emphasized personalized treatment strategies for CSU. Current guidelines have not yet integrated emerging therapies like omalizumab, remibrutinib, and dupilumab. Omalizumab, the only biologic currently approved for CSU, has demonstrated strong efficacy, achieving good control in 51.9% of patients and complete control in 35.8% of patients at the highest dose (300 mg). However, concerns over its black box warning for anaphylaxis have contributed to underutilization, even though the risk is rare (0.09%-0.2%) and mostly occurs within 2 hours of initial injections in patients with prior anaphylaxis history.

New treatments like remibrutinib, rilzabrutinib, and dupilumab offer hope for improved CSU management. In the REMIX-1 and -2 trials, remibrutinib achieved UAS7 scores of 6 or less in 11.9% more patients than placebo, demonstrating rapid onset and sustained response over 52 weeks, with additional improvements in sleep and weekly itch severity (AIS7). Its safety profile includes mild adverse events like nasopharyngitis (6.6%), headache (6.1%), and petechiae (3.8%). Dupilumab, evaluated in the phase 3 Liberty-CUPID Study C, showed significant benefits over placebo, including greater reductions in itch severity, UAS7 scores, and improved disease control, with 30% achieving complete response. Dupilumab's adverse events were primarily skin-related. These advancements, including ongoing FDA reviews, signal a new era in CSU therapy, with the potential for better disease control and enhanced quality of life for patients.