The use of biologic therapy for the treatment of patients with chronic spontaneous urticaria (CSU) is positioned to become even more prominent as more data become available. Current and emerging biologic therapies for patients with CSU were discussed in a presentation at the 2024 Fall Clinical Dermatology Conference.

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

Almost all the new agents that are being investigated for CSU are considered to be biologics, some of which were discussed by Brad P. Glick, DO, MPH, FAAD, David Lang, MD, FAAAAI, and Dawn L. Merritt, DO, FAAD, FAOCD, in a CME satellite symposium on evolving therapies for CSU at the recent 2024 Fall Clinical Dermatology Conference.

Omalizumab has changed the face of treatment for CSU more so than any other drug. The potential use of omalizumab for CSU was discovered while we were doing basic research on CSU and observed that some patients with the disease had an IgG autoantibody directed against the IgE receptor. We studied that antibody, and we learned that it activated both basophils and mast cells and caused the secretion of histamine. It looked like we were dealing with an autoimmune cutaneous disease, at least in a subpopulation of patients. The antigen was the IgE receptor, and there was literature at the time indicating that the IgE receptor level is proportional to the circulating IgE level. So, if you lowered the IgE level, you would also lower the IgE receptor level; if lowered enough, the autoantibody would not work because it would not be able to cross-link receptors on the cell surface. That was the theory behind it, although it is actually more complicated than this. Omalizumab was already marketed for asthma at that time, and we knew that it could lower IgE levels and therefore, theoretically, could decrease the IgE receptor level.

We then conducted an investigator-initiated trial with 12 patients who had very severe cases of CSU that were not easily treatable. We took these patients off steroids, treated them with omalizumab, and found that hives stopped in 7 of them during the course of the study, an improvement in symptoms occurred in 4 patients, and treatment failure occurred in 1 patient. That was 11 successes and 7 striking successes in 12 patients. Phase 2 and 3 studies followed this trial, and these data were submitted to the US Food and Drug Administration (FDA), and that is when omalizumab was approved for the treatment of CSU. It was a tremendous success for patients with CSU, and it changed the entire course of treatment for the disease.

Dupilumab, which was also discussed at the 2024 Fall Clinical Dermatology Conference, is a biologic that simultaneously blocks the signaling of IL-4 and IL-13. Those interleukins are important for the synthesis of IgE. Dupilumab is one of the only drugs that I have seen for patients with CSU where there was a proportion of responders whose hives did not come back when the drug was stopped after approximately 6 months of therapy, as shown in the LIBERTY-CSU CUPID A and B studies. In these studies, patients stopped dupilumab at 24 weeks, and, when you look at the follow-up data up to 36 weeks, you can see that the curve stayed similar. In other words, you had another 12 weeks, and you did not see a worsening of symptoms. Conversely, the phase 3 GLACIAL, ASTERIA I, and ASTERIA II trials of omalizumab found that when it is stopped after 12 to 24 weeks of therapy, most symptoms return to baseline levels over the following 16 weeks, so patients need to stay on it. Since the percent success rate with dupilumab may be a little lower than that with omalizumab, dupilumab may not supplant omalizumab; however, it would be another good drug to add to our armamentarium if it is FDA approved.

Biologic therapy in CSU is really the wave of the future and, in my opinion, will ultimately replace the use of cyclosporine. In the next couple of years, I think that we will be talking about which biologic is the best for a patient and in what sequence. Also, it would be interesting if we had a biologic that worked extremely well and was also fast, oral, and inexpensive so that you could potentially supplant the use of antihistamines.