Many patients with chronic spontaneous urticaria (CSU) are refractory to or achieve suboptimal outcomes with currently available therapies, so there is a gap in current therapies. At the 2024 Fall Clinical Dermatology Conference, a CME satellite symposium discussed recent clinical trial data with emerging treatments for CSU, including those targeting BTK and IL-4Rα.

Following this symposium, featured expert Jonathan A. Bernstein, MD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Bernstein’s clinical perspectives on the discussion are presented here.

Emerging therapies for CSU were discussed at the recent 2024 Fall Clinical Dermatology Conference by Brad P. Glick, DO, MPH, FAAD, David Lang, MD, FAAAAI, and Dawn L. Merritt, DO, FAAD, FAOCD, during a CME satellite symposium. The emerging treatments that are furthest in development for CSU target BTK and IL-4Rα, but therapies targeting mast cell receptors such as KIT, MRGPRX2, and SIGLEC8 are also highly of interest and in development.

One study that was mentioned during the session was the phase 3 LIBERTY-CSU CUPID Study A, which looked at dupilumab, an anti–IL-4Rα antibody. The study showed that patients who received dupilumab vs placebo had a significant and clinically meaningful improvement in the Itch Severity Score (ISS7), the Urticaria Activity Score (UAS7), and the Hives Severity Score (HSS7) at week 24 of treatment. Treatment was then stopped, and patients were followed until week 36, and there was a sustained treatment effect with dupilumab. Dupilumab does not put patients into remission and is not curative, but it may give them a sustained response. This may be important if a patient misses a dose here and there; in patients whose disease is controlled, you could also potentially spread out the dosing frequency to be every 4 weeks instead of every 2 weeks, but this still needs to be further studied.

Results from the REMIX-1 and REMIX-2 studies examining the BTK inhibitor remibrutinib were also discussed at the 2024 Fall Clinical Dermatology Conference CME satellite symposium. In these studies, significantly more remibrutinib-treated patients achieved a UAS7≤6 at week 12 compared with those receiving placebo. After 24 weeks of treatment, patients on placebo were transitioned to receive remibrutinib and had similar improvements in UAS7≤6 as those already receiving remibrutinib to week 52. REMIX-1 also looked at the impact of remibrutinib on sleep and daily activities and found improvement with remibrutinib compared with placebo.

One category of emerging agents that was not discussed much during the CME satellite symposium but I think is important are KIT-targeted treatments. At the American College of Allergy, Asthma & Immunology 2024 Annual Scientific Meeting, my group presented some recent phase 2 data on barzolvolimab, an anti-KIT antibody, for patients with chronic inducible urticaria (ie, cold urticaria and symptomatic dermographism) that look very promising. However, there are some side effects that have to be further evaluated that include transient neutropenia and changes in hair color.

In the future, I think that we will have several more choices for therapies to use after antihistamines in addition to omalizumab. Therefore, CSU-treating clinicians will have to determine which patients would be more likely to respond or not respond to these newer agents, similar to what has been elucidated for omalizumab over the years. As we learn more about mast cell pathophysiology, biomarkers, and other predictors of treatment response, we will continue to develop an improved understanding of how to optimize the treatment of this chronic disease. Stay tuned for updated US and international CSU guidelines that are presently being developed. For the United States, this will be the first updated guideline by the Joint Task Force on Practice Parameters since 2014. Fortunately, the US guideline will be a living document, meaning that there will be more frequent updates as therapies become approved by the US Food and Drug Administration (FDA) and as we gain more experience with how to use these medications and with where they should be placed in the CSU treatment algorithm.