What Are New Treatments for Chronic Spontaneous Urticaria?

If you have tried standard therapies like high-dose antihistamines (up to four times the standard dose of second-generation, non-sedating antihistamines under a doctor’s supervision) and omalizumab (Xolair) but still have daily hives, you are not out of options. For patients with refractory (treatment-resistant) chronic spontaneous urticaria (CSU), guidelines outline further steps, and the treatment landscape now includes newly approved targeted therapies and investigational drugs in clinical trials.

Note: This page is for diagnosed CSU. If you experience trouble breathing, swelling of the throat or tongue, faintness, or rapidly progressive swelling, seek emergency medical care immediately, as these may be signs of anaphylaxis. Additionally, if your individual hives last longer than 24 hours, are painful, or leave bruises, tell your doctor, as this may require evaluation for conditions other than CSU.

The Guideline Option: Cyclosporine

According to international treatment guidelines, if your hives are not controlled by up-dosed antihistamines and omalizumab, the next step is often cyclosporine ^[1][2].

Cyclosporine is an oral immunosuppressant that works by reducing the overall immune response causing your hives. Research shows that a low-dose daily regimen can successfully control CSU in a substantial proportion of people who did not respond to omalizumab ^[3][1]. However, the use of cyclosporine for CSU is off-label in many countries, meaning it is not officially approved by regulatory agencies specifically for this condition.

Because cyclosporine suppresses the immune system, it is generally reserved for severe cases and requires close medical supervision. It can cause elevated blood pressure (hypertension) and reduce kidney function ^[4][1]. Baseline and ongoing blood and urine tests are required, and the medication may not be suitable if you have pre-existing kidney disease or uncontrolled blood pressure. Due to these risks, cyclosporine is often used as a temporary intervention rather than a lifelong treatment, and hives may return after stopping ^[5][6].

Newly Approved Therapies

If cyclosporine is not appropriate, or if you prefer a different approach, recent regulatory approvals have introduced new medications for CSU. (Approval status varies by country; check with your specialist about availability in your area).

Remibrutinib

Remibrutinib is an oral pill taken twice daily. It was recently approved in the U.S. (September 2025) and some other jurisdictions for adults with CSU inadequately controlled by H1-antihistamines ^[7]. It belongs to a class of drugs called BTK inhibitors. Bruton’s tyrosine kinase (BTK) is an enzyme inside mast cells and basophils. By blocking BTK, remibrutinib stops these immune cells from releasing histamine ^[8].

Clinical trials showed that remibrutinib can act quickly, with about 28% to 32% of patients achieving a complete response (zero hives and itch) by 24 weeks ^[9][10]. While generally well-tolerated, important safety concerns include the risk of liver enzyme elevations, which requires monitoring of your liver function ^[11]. Other reported side effects include upper respiratory tract infections, headaches, and petechiae (tiny, non-raised red or purple spots on the skin) ^[12][10]. You should contact your doctor immediately if you develop signs of serious infection, unusual bleeding or bruising, or liver injury (such as yellowing of the skin or eyes).

Dupilumab

Dupilumab is an injectable biologic therapy (a drug made from living organisms that targets specific parts of the immune system). It binds to the IL-4 receptor alpha subunit, which blocks inflammatory signaling from two key proteins: IL-4 and IL-13 ^[13]. It was recently approved for CSU in the U.S. (April 2025) and Japan ^[14][15].

Dupilumab has an established safety profile from its use in other allergic conditions; common side effects include injection-site reactions and eye inflammation (conjunctivitis) ^[16]. However, its effectiveness specifically in patients who have previously failed omalizumab is mixed. In a Phase 3 trial dedicated to patients who were omalizumab-intolerant or incomplete responders, dupilumab missed its primary endpoint, though some patients did see numerical improvements ^[17]. Real-world data suggests it can provide significant relief for a subset of these patients, but it is not guaranteed to work for everyone with omalizumab-resistant disease ^[18].

Investigational Treatments in Clinical Trials

If currently available therapies do not work, you may consider participating in a clinical trial for investigational drugs. You can search for recruiting trials in your area on registries like ClinicalTrials.gov.

Barzolvolimab

Barzolvolimab is an investigational anti-KIT antibody—a biologic drug designed to directly deplete the overactive mast cells in the skin ^[10].

In Phase 2 clinical trials, barzolvolimab demonstrated strong results across patient groups, including those who had previously failed omalizumab ^[19]. At the most effective dose tested, 51.1% of patients achieved completely clear hives (a UAS7 score of 0) after 12 weeks ^[19]. It is currently in larger Phase 3 trials to confirm these results and establish long-term safety. Researchers are monitoring unique side effects observed in early trials, such as reversible changes in hair color (dark hair turning lighter) and a temporary decrease in certain white blood cells (neutropenia) ^[19][10].

Discontinued Experimental Drugs

When researching CSU treatments online, you may see articles mentioning other drugs. It is important to know that ligelizumab did not meet its key Phase 3 efficacy endpoints for CSU, and its development for this condition was discontinued ^[20][14]. Similarly, lirentelimab development for CSU was halted after early trials due to a lack of sufficient efficacy ^[21][15].