Sequencing Emerging Therapies in CSU, With Jonathan Bernstein, MD

Jonathan Bernstein, MD, professor of medicine at the University of Cincinnati and physician with Bernstein Allergy Group and the Bernstein Clinical Research Center, outlined how clinicians may approach treatment sequencing in chronic spontaneous urticaria (CSU) as newer targeted therapies expand options beyond antihistamines and omalizumab. Speaking with HCPLive virtually during the 2026 Eastern Allergy Conference (EAC) in Palm Beach, Florida, Bernstein emphasized that treatment selection should remain individualized despite forthcoming guideline recommendations.

“If they [have] never been treated, then we're going to start using high-dose antihistamines to make sure they truly are not ineffective,” he said.

He added that this first trial of second-generation antihistamines should include dose escalation up to 4 times the standard recommended dose. He noted that some patients may not have used antihistamines consistently or appropriately before referral, making confirmation of treatment failure an important first step.

Bernstein indicated that updated CSU guidelines are expected to continue recommending omalizumab as the preferred next-line therapy based on the strength and certainty of available evidence, as well as its established safety profile. Although omalizumab carries a boxed warning for anaphylaxis, he noted that concerns largely stem from reports in asthma populations rather than patients with urticaria.

However, Bernstein emphasized that guideline recommendations may not be appropriate for every patient. Individuals with very low immunoglobulin E (IgE) levels and evidence of autoimmune disease may represent a distinct phenotype that could warrant consideration of alternative therapies, including dupilumab or remibrutinib.

He noted that biomarkers are not expected to be incorporated into formal treatment algorithms because evidence supporting biomarker-guided decision-making remains limited. Nevertheless, Bernstein encouraged clinicians to recognize differences among patients and consider how biomarkers may eventually help identify treatment-responsive subgroups.

Cyclosporine remains an option for patients with difficult-to-treat disease, particularly those with chronic autoimmune urticaria, according to Bernstein. However, he noted its use requires monitoring for adverse effects, including hypertension and renal toxicity, and it is expected to occupy a later position in treatment algorithms as biologic and targeted therapies become more widely available.

Bernstein also highlighted the importance of obtaining biomarker assessments before initiating omalizumab when testing is planned. He explained that measurements such as total IgE, thyroid peroxidase antibodies, the CU Index, and basophil activation testing can potentially help characterize disease subtypes, but results may be affected once omalizumab therapy begins.

As treatment options continue to expand, Bernstein said additional real-world evidence and controlled studies will be needed to clarify how biomarkers and patient phenotypes can inform therapeutic sequencing in CSU.

References

Bernstein J. CSU biomarkers and advanced treatments. Poster presented at EAC 2026 on May 29.