The treatment landscape for chronic spontaneous urticaria (CSU) is rapidly expanding with the emergence of more targeted therapies. Investigational therapies with new mechanisms of action and tailored management based on patient characteristics may help address unmet needs for patients with CSU, as discussed at the 2026 AAAAI Annual Meeting.

Following this presentation, featured expert Jonathan A. Bernstein, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr Bernstein on these findings are presented here.

As the treatment landscape for CSU continues to evolve, new targeted therapies are expanding the options for patients who do not respond to high-dose nonsedating H₁ antihistamines. This is an interesting time. Targeted therapies for CSU help us understand the disease’s pathogenesis better because we can see how relevant some of these targets are.

The reason omalizumab tends to be positioned a little ahead of dupilumab and remibrutinib is because it has been out for so long. We have a lot of experience with and safety data for this agent for the treatment of CSU. When it first became available, there was a boxed warning for anaphylaxis, and then that warning was commuted. Now, patients receive the first 2 or 3 injections with an observation period in the office, and omalizumab can be self-administered thereafter. We also have a lot of safety data for dupilumab across multiple indications, but it was only recently approved by the US Food and Drug Administration (FDA) for CSU in April 2025. We do not have as much data on remibrutinib, as it was just FDA approved for CSU in September 2025.

If you have patients with CSU who are not responsive to omalizumab, rather than increasing the dose or frequency of omalizumab, dupilumab or remibrutinib might be more appropriate. But, again, if you are the person who orders some of these biomarkers before starting therapy, such as getting a total IgE, a Chronic Urticaria (CU) Index, and an anti-TPO, and they are indicative of chronic autoimmune urticaria—the total IgE is very low, less than 2 IU/mL, while the others are elevated—I do not think that you should feel compelled to start omalizumab.

Based on the data that I have seen already and the data that are forthcoming, I think that this makes sense. However, I know that everyone works differently and has different thought processes. That is what makes medicine somewhat of an art and not always a science. There are clinical decision algorithms that are going to vary based on people’s experiences with using a drug, patient preferences and values, and the drug’s affordability, among other factors.

Another area of interest is KIT inhibition. So far, the data look promising, and patients are improving. Indeed, early data from Martin Metz, MD, et al from their ongoing, phase 2, open-label extension study presented at the 2026 AAAAI Annual Meeting showed that treatment with the anti-KIT antibody briquilimab results in the rapid and durable control of CSU (abstract 73). However, the concern with KIT inhibitors is side effects, including the graying of the hair roots, the hypopigmentation of the skin, taste perversion, and transient neutropenia. For the most part, these seem to resolve over time during treatment—except for the graying of the hair. Because of their side-effect profile, I anticipate that KIT inhibitors may not be used immediately after high-dose nonsedating H₁ antihistamines, should they receive FDA approval for CSU in the future. However, if patients have more refractory disease, that may be when these agents are recommended.

Even with all these new targeted therapies, some patients still do not respond. There may be other pathways involved, including the MRGPRX2 receptor, or maybe there are other ways of activating mast cells that we do not understand. Perhaps there is a role for basophils, for example. There are a lot of factors that may be contributing to CSU that are not clearly understood, given the disease’s complex pathogenesis.