The field of chronic spontaneous urticaria (CSU, also known as chronic hives) treatment has long progressed slowly.
For years, options for antihistamine-resistant cases were limited - mainly omalizumab (approved in 2014), corticosteroids, cyclosporine, or other alternatives - while other allergic conditions like asthma and atopic dermatitis saw rapid advances with new biologics and small molecules.
Recent breakthroughs are finally accelerating change. In the past year, the FDA approved dupilumab (Dupixent) in April 2025 and remibrutinib (Rhapsido, the first oral BTK inhibitor for CSU) later in 2025 for antihistamine-refractory CSU. These expand targeted options beyond omalizumab, with more agents (such as c-KIT and MRGPRX2 antagonists) on the horizon.
A key challenge has been understanding CSU's heterogeneity.
Some patients have an autoimmune endotype (e.g., type IIb with low IgE and IgG autoantibodies to FcεRI), while others show different patterns.
Omalizumab works well for many, especially those with higher baseline total serum IgE, but less reliably in low-IgE subgroups, where responses may be delayed or absent.
Negative prognostic factors like high C-reactive protein, eosinopenia, and basopenia link to greater severity and longer disease duration.
Predictive biomarkers are emerging: higher IgE predicts better/faster omalizumab response, while very low IgE, basopenia, or certain indices signal poorer control after 12 weeks.
A recent retrospective analysis (Le et al.) highlights that patients with low IgE (≤40 IU/mL), basopenia, or positive chronic urticaria index were more likely to have poorly controlled symptoms on omalizumab.
Encouragingly, newer therapies like dupilumab and remibrutinib show benefit across high- and low-IgE patients, potentially replacing older agents like cyclosporine for omalizumab non-responders.
The path ahead emphasizes:
- identifying endotypes
- validating point-of-care biomarkers (positive and negative)
- refining trials to guide personalized treatment.
With these recent approvals and ongoing research, the long, winding road to better CSU management is finally gaining momentum - offering real hope for patients with refractory disease.
References:
https://www.jaci-inpractice.org/article/S2213-2198(26)00001-2/fulltext