Q&A: Jonathan Bernstein, MD, FAAAAI, Discusses Advances in Chronic Spontaneous Urticaria Treatments and AAAAI Data

At the recent 2025 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress, Jonathan Bernstein, MD, FAAAAI, presented multiple abstracts on the efficacy of rilzabrutinib in chronic spontaneous urticaria (CSU).^1-2

In addition, Bernstein authored an abstract outlining findings from the LIBERTY-CSU CUPID Study A and Study C phase 3 trials evaluating dupilumab (Dupixent; Regeneron and Sanofi) in patients with CSU who remain symptomatic despite H1-antihistamine treatment.³

In a Q&A with Dermatology Times, Bernstein, a physician practicing in Cincinnati, Ohio, explored the studies and their key insights, their clinical impact on dermatologists and allergists, and the implications for the future of CSU treatment.

Jonathan Bernstein, MD, FAAAAI

Q&A

Q: Your poster at the AAAAI meeting presented real-world treatment patterns among patients with CSU initiating advanced therapies. What key insights emerged from these findings, and how might they impact clinical practice?

A: In our retrospective analysis, we observed several noteworthy findings. First, add-on therapies were used in the majority of patients across all subgroups, including patients treated with omalizumab (55.9%), which was the most dispensed advanced therapy, systemic anti-inflammatory agents (51.9%), and systemic immunosuppressants (52.9%).

Additionally, the proportion of patients switching treatments was higher with systemic anti-inflammatories (44.3%) and systemic immunosuppressants (51%), compared to omalizumab (16%). However, more than a quarter of all omalizumab-treated patients (26.2%) were being prescribed higher than FDA-approved doses.

Ultimately, the findings suggest that, despite current treatment options, there is still a significant need for new advanced therapies that can more adequately control CSU symptoms.

Q: How does your research on CSU and advanced therapies address the evolving landscape of treatment options for patients who are unresponsive to conventional therapies?

A: Despite significant advancements, unmet needs remain for people suffering from CSU. The disease remains uncontrolled in up to 50% of patients, who continue to experience debilitating symptoms such as intensely itchy recurrent hives, swelling or both, which can significantly impact their day-to-day lives and quality of life.

Over time, we’ve learned multiple mechanisms can cause the inflammation underlying CSU, and consequently, patients have different needs or respond differently to treatments. Our goal with research is to better understand how patients are responding to existing advanced therapies, assess certain treatment patterns that can help us better address gaps in care, and further explore investigational medicines – targeting these different mechanisms – that could potentially fill these unmet needs.

Q: Could you elaborate on the significance of real-world data in the management of CSU, especially in the context of biologics and other advanced treatments?

A: As the treatment paradigm in CSU evolves, real-world data will be essential to understanding how different segments of patients respond to different therapeutic approaches, particularly new and emerging medicines. As mentioned above, real-world evidence will also help provide continued line of sight into unmet patient needs that we seek to address in clinical research.

Q: Rilzabrutinib, a novel oral BTK inhibitor, is being investigated in CSU. What are your thoughts on the potential role of rilzabrutinib in treating CSU patients?

A: Further research will be needed to fully understand the potential role of rilzabrutinib, but early data has suggested it could hold promise as a future treatment option for patients with moderate to severe CSU.

In an earlier readout from the RILECSU phase 2 study, rilzabrutinib significantly reduced itch, hives and urticaria in adult patients with moderate to severe CSU, demonstrating its potential to make a meaningful difference in CSU symptom control.

Additionally, the data presented at AAAAI, which showed treatment with once-daily oral rilzabrutinib was associated with significant and sustained improvements in angioedema outcomes in this same population, further support the earlier findings.

Q: With the increasing prevalence of CSU, what challenges do you face when selecting treatment strategies for diverse patient populations, and how do your findings aim to address these challenges?

A: Some of the biggest challenges that exist include access barriers to advanced therapies, as well as difficulties in diagnosing CSU in people with skin of color. It’s also worth noting that racially diverse patients can be underrepresented in clinical trials.

Given these challenges, real-world evidence is critical to understanding treatment patterns and outcomes for certain populations, which in turn, may help us make the case for more accessible advanced treatments.

References

1. Bernstein J, Lee CH, Ferrucci S, et al. Effects of rilzabrutinib on angioedema over 12 weeks: Results from the phase 2 RILECSU trial in participants with moderate-to-severe chronic spontaneous urticaria. Abstract presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA.
2. Talia J, Sarbjit S, Lee CH, et al. Rilzabrutinib improves chronic spontaneous urticaria in patients with and without allergic comorbidities: A subgroup analysis from the RILECSU study. Abstract presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA.
3. Casale T, Saini S, Bernstein J, et al. Dupilumab improves itch and urticaria activity in patients with chronic spontaneous urticaria: Pooled results from two phase 3 trials (LIBERTY-CSU CUPID Study A and Study C). Abstract presented at: 2025 AAAAI/WAO Joint Congress; February 28-March 3, 2025; San Diego, CA.