Although biomarkers are currently not routinely used in the management of chronic spontaneous urticaria (CSU), recent research demonstrates that there are some biomarkers that may help identify patients who are most likely to respond to treatment and could help guide management decisions. Some of this research was discussed in a presentation at the 2024 Fall Clinical Dermatology Conference.

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

We have always been interested in understanding which patients with CSU will respond to treatment and which patients will not, as well as whether biomarkers could help predict response. The study of biomarkers in CSU grew with the development of biologics; however, a lot of work went into studying biomarkers even with antihistamines. For example, biomarkers such as C-reactive protein (CRP) have been evaluated in CSU, with some evidence suggesting that a patient with CSU who has a high CRP level will not be as responsive to antihistamines, although the results have not been consistent.

With omalizumab, multiple biomarkers have been evaluated, including total IgE, eosinophils, basophils, and autoantibodies, specifically thyroid peroxidase (TPO) autoantibodies. In a CME satellite symposium at the 2024 Fall Clinical Dermatology Conference, Brad P. Glick, DO, MPH, FAAD, David Lang, MD, FAAAAI, and Dawn L. Merritt, DO, FAAD, FAOCD, discussed the findings of a study showing that serum total IgE levels were higher in omalizumab complete and partial responders vs nonresponders. I think that it is important to test for IgE prior to treatment with omalizumab, because if you have a patient with a very low IgE level, you can set expectations for them that they may not respond as well or as quickly to treatment. Another biomarker that is probably better than most is the TPO autoantibody. The presence of TPO autoantibodies has been shown to correlate with a poor response to omalizumab. We have also looked at other biomarkers such as the basophil activation test and the Chronic Urticaria Index that may have some utility as well.

Now, will these biomarkers be relevant for the newer therapies that are being developed for CSU? I think that they might be for dupilumab, but it is unclear to me whether they will be relevant for other medications that work on targets further downstream such as BTK (eg, remibrutinib) or on selective mast cell receptors such as c-KIT. Because, while omalizumab works at the cell surface to cause dissociation of IgE from its receptor and downregulaion of IgE receptors, BTK and c-KIT involve different pathways for mast cell activation. If you knock them down, the cells will not respond normally, and, in the case of c-KIT, you could potentially kill the cell. There are also other pathways that could be targeted to reduce mast cell burden, where the current biomarkers we have may not be as relevant for novel therapies that target these different pathways. So, we will have to conduct additional studies to examine these predictive biomarkers for these investigational drugs once approved by the US Food and Drug Administration (FDA).

I think that many of us are constantly looking for better ways to predict treatment response for when we arrive at a crossroads for deciding which treatment direction to pursue after antihistamines. I also think that there will be several therapeutic choices available within the next couple of years, so there could potentially be a greater role for biomarkers in the future that predict best treatment.