Mark Scarupa, MD 

Future Directions of the CSU Treatment Landscape

Each of the available therapies for CSU has their own strengths and limitations. Omalizumab, having been used for many years, benefits from extensive clinical experience and long-term safety data. Remibrutinib offers the advantage of being an oral medication and shows promise, especially in patients who have not responded well to omalizumab. Barzolvolimab appears to be a highly potent option, also demonstrating efficacy in patients with prior treatment failures. Presenting all these options to patients and discussing the pros and cons allows for shared decision-making tailored to individual preferences and needs.

For allergists, dermatologists, and general physicians treating CSU, it is crucial to be knowledgeable about all available therapies to provide comprehensive care. Although these treatments may have adverse effects, their safety profiles are generally favorable. Patient education is equally important: Many patients are frustrated by misconceptions about their disease, such as the belief that diet or environmental factors are the cause. Providing clear explanations about CSU’s underlying mechanisms can help patients better understand the fluctuating nature of their symptoms and improve their ability to manage the condition day to day.

After 2 decades of clinical practice, it is clear that therapies like omalizumab have transformed CSU management, yet there remain patients whose condition is not fully controlled or who cannot use certain drugs. The ongoing development of new treatment options is therefore very encouraging, offering hope for more personalized and effective care. The significant investment in CSU research by pharmaceutical companies is a positive sign for the future, promising an expanding tool kit to help patients achieve better disease control and quality of life.

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A panelist discusses how each chronic spontaneous urticaria (CSU) therapy—omalizumab with its extensive safety record, oral remibrutinib for omalizumab nonresponders, and potent barselolizumab for treatment-resistant cases—offers unique benefits and limitations, emphasizing the importance of shared decision-making and patient education to dispel misconceptions and tailor care.

CSU: Long-Term Disease Control

Long-term studies of omalizumab in CSU have demonstrated that although the treatment is very effective during use, symptoms tend to return almost universally once the drug is discontinued after 6 months to 1 year. In contrast, data from barselolizumab trials show a promising difference: Between 48 and 76 weeks, more than a third of patients remained symptom free even after stopping treatment. This suggests that barselolizumab might contribute to a higher rate of sustained remission, potentially shortening the overall disease duration for patients.

The encouraging findings from barselolizumab raise the possibility of using this therapy more broadly to achieve longer-lasting disease control and remission in CSU. Such an approach could shift treatment goals from merely managing symptoms to actually modifying the course of the disease. This represents an important advancement compared with existing therapies, where ongoing treatment is often necessary to maintain symptom control.

The phase 2 clinical trial for barselolizumab followed a typical design for CSU studies, using a 12-week primary end point focused on reducing urticaria severity and activity. The trial results showed a highly significant improvement in the treatment group compared with placebo at 12 weeks, reinforcing the drug’s strong therapeutic potential early in the treatment course.

A panelist discusses long-term omalizumab studies showing symptom relapse after discontinuation, contrasting this with barselolizumab data where over a third of patients remained symptom free months after stopping treatment, suggesting potential for sustained remission and disease modification in chronic spontaneous urticaria (CSU).

Phase 2 Results for Barzolvolimab for CSU Treatment

There has been significant excitement around anti-KIT therapies for CSU, with broad agreement that they may become the most potent treatments available. Early-phase clinical trials, including phase 1 and 2, have shown remarkable efficacy, with anti-KIT drugs like barselolizumab demonstrating a degree of symptom control that exceeds other treatments. Notably, data presented at a recent AEACI meeting revealed that many patients who stopped treatment after 48 weeks remained symptom free months later, suggesting the possibility that these therapies may be disease modifying and could accelerate remission in some individuals.

The data from barselolizumab, in particular, have generated enthusiasm due to its strong and sustained treatment effects observed in phase 2 trials. Compared with other existing and pipeline therapies, barselolizumab has shown numerically superior results in achieving symptom control and patient well-being. Although direct trial comparisons are imperfect, the consistently positive outcomes position anti-KIT therapies as a highly promising advancement in CSU treatment.

In terms of quality of life, effective control of CSU symptoms can significantly alleviate the burden of this often debilitating condition. Barselolizumab’s broad efficacy means it has the potential to improve quality of life for a larger proportion of patients. Although other therapies like remibrutinib or omalizumab also improve quality of life for responders, barselolizumab’s wider impact may benefit more patients overall, offering new hope for better disease management.

A panelist discusses the promising potential of anti-KIT therapies, especially barselolizumab, in chronic spontaneous urticaria (CSU) treatment, and highlights their superior efficacy, possible disease-modifying effects, and the potential to improve quality of life for a broader range of patients compared with existing options.

Remibrutinib for CSU Treatment

The speaker shares their involvement in the clinical trials for remibrutinib, an oral therapy for CSU. The drug demonstrated a reduction in urticaria activity at 12 weeks that was comparable to the standard of care, omalizumab. A key advantage of remibrutinib is its oral formulation, which offers convenience, and it shows a rapid onset of action, similar to that of omalizumab and other emerging therapies. However, there is still limited experience with remibrutinib, particularly in specific populations such as women who may be pregnant or planning pregnancy.

Looking ahead, the clinician plans to first use remibrutinib in patients who have not responded fully to omalizumab or who have experienced omalizumab treatment failure altogether. Additionally, it may be a strong option for patients who prefer an oral treatment over injectable biologics. This approach will allow for early assessment of the drug’s performance in real-world settings, helping to gauge how well its clinical trial results translate into everyday practice.

If remibrutinib proves to be as effective in practice as it was in trials, it is expected to become a routine alternative to omalizumab in the CSU treatment algorithm. Ultimately, offering it alongside existing options would empower patients to choose a therapy that best fits their preferences and needs, improving patient satisfaction and potentially treatment adherence.

A panelist discusses the potential of remibrutinib as an effective oral alternative to omalizumab for chronic spontaneous urticaria (CSU), noting its rapid onset, promising trial results, and anticipated use in patients who prefer oral therapy or have not responded to biologics.

Mark Scarupa, MD

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