The Evolving CSU Pipeline: Biologics, BTK Inhibitors, and Biomarker-Guided Care

As understanding of the immune-mediated pathophysiology of chronic spontaneous urticaria (CSU) has evolved, treatment has increasingly shifted from broad symptom control toward targeted therapies. Nicholas Brownstone, MD, board-certified dermatologist at Mount Sinai, discussed current treatment options and emerging approaches for patients with CSU.

Antihistamines remain part of CSU treatment guidelines and can help control pruritus, but Brownstone noted that these medications primarily address symptoms rather than the underlying disease process. Their potential for sedation can also be problematic for some patients. Greater understanding of the immune mechanisms involved in CSU has led to targeted therapies designed to address the condition more directly.

“Like psoriasis, hidradenitis suppurativa, and atopic dermatitis, the more we dive into the pathophysiology of the disease, the better our treatments are getting and the more targeted treatments we're able to offer our patients,” he said.

Currently, Brownstone highlighted 3 FDA-approved therapies for CSU: dupilumab, an IL-4 and IL-13 inhibitor; remibrutinib, a Bruton tyrosine kinase (BTK) inhibitor; and omalizumab, an IgE inhibitor. These therapies target different components of the immune-mediated pathways underlying CSU and offer effective treatment options with favorable safety profiles. Remibrutinib may be particularly relevant for patients seeking rapid symptom improvement, with clinical benefits beginning within approximately 1 to 2 weeks, according to Brownstone.

Despite these advances, additional treatment options are needed, and the CSU therapeutic pipeline includes several novel mechanisms. Investigational approaches include additional BTK inhibitors as well as therapies targeting KIT, thymic stromal lymphopoietin (TSLP), and Mas-related G protein-coupled receptor X2 (MRGPRX2). These approaches could expand treatment options for patients who do not achieve adequate control with currently available therapies.

Brownstone also pointed to biomarker-guided treatment selection as a potential future direction. Given the heterogeneity of immune mechanisms involved in CSU, identifying biomarkers that characterize an individual patient's disease could eventually allow clinicians to select therapies according to a patient's specific immune profile. Such an approach could move CSU management toward greater personalization, similar to treatment strategies emerging in other inflammatory dermatologic diseases.

"What I love about dermatology and what I love about CSU is the amount of innovation that's going on,” Brownstone noted.

For clinicians evaluating patients with urticaria, he emphasized the importance of distinguishing acute urticaria, CSU, and chronic inducible urticaria through careful history-taking. He also encouraged dermatologists to routinely assess the broader impact of disease by asking whether symptoms are affecting patients' quality of life or mental health, including anxiety, depression, and sleep. These simple questions can help identify patients experiencing a substantial burden and guide more comprehensive management.

Missed part 1 of the conversation? Click here.