Emerging Therapies for Chronic Spontaneous Urticaria
Chronic spontaneous urticaria (CSU) treatment is rapidly evolving, along with the implications for clinical practice, wrote authors of a recent narrative review in Current Opinion in Allergy and Clinical Immunology.
CSU affects patients worldwide and is characterized by recurrent hives and/or angioedema lasting >6 weeks without an identifiable trigger. Historically, second-generation H1 antihistamines and, more recently, the anti-IgE monoclonal antibody omalizumab have dominated management. However, emerging evidence now supports a broader therapeutic landscape.
The review outlines multiple novel agents in late-stage clinical development for CSU. Among these, omalizumab biosimilar CT-P39 has secured approval from the EMA and US FDA, providing a potentially more accessible anti-IgE option. Dupilumab, an IL-4/IL-13 pathway inhibitor, has also been approved in Japan and the US for CSU, offering an alternative mechanism of action. Remibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, has also received FDA approval. Additionally, anti-KIT monoclonal antibodies such as barzolvolimab are moving through phase 3 development.
Not all candidates have progressed; ligelizumab, benralizumab, and the MRGPRX2 antagonist EP-262 have been discontinued for CSU indications. The authors noted a shift from a one-size-fits-all “anti-IgE era” toward a more tailored approach, aligning therapies with patient profiles and specific disease mechanisms.
Clinical Implications for Healthcare Professionals
For allergists, immunologists, dermatologists, and primary care clinicians managing CSU, these developments herald a significant shift in therapeutic strategy, the authors stated. The approval of multiple agents with distinct immunologic targets allows clinicians to consider mechanism-based sequencing or combination approaches for patients inadequately controlled with antihistamines or omalizumab.
Dupilumab’s efficacy highlights the role of type 2 inflammation beyond IgE, aligning with mechanistic insights into CSU pathophysiology. BTK inhibitors like remibrutinib offer an oral targeted option, which may increase patient adherence and broaden CSU management beyond injectable biologics. As further data mature, clinicians should integrate phenotype and endotype characterization into treatment decisions, potentially through clinical scoring tools or biomarkers, to optimize outcomes.
Real-world implementation will necessitate updates to practice guidelines and patient education on emerging options, side effect profiles, and monitoring requirements. Moreover, evolving evidence will clarify where small molecules vs biologics best fit within CSU care pathways.
Reference:
Wedi B. Biologic and small molecule therapies in chronic spontaneous urticaria: an update. Curr Opin Allergy Clin Immunol. 2025;25(5):418-425. doi:10.1097/ACI.0000000000001095.
