CHRONIC spontaneous urticaria (CSU) is a distressing inflammatory skin condition characterised by the recurrent appearance of hives, angioedema, or both, lasting more than six weeks without an identifiable cause. This condition significantly affects patients’ quality of life, disrupting sleep, emotional wellbeing, and daily functioning.
Current treatments include second-generation H1-antihistamines, but up to half of patients fail to respond adequately, even at increased doses. Omalizumab, an anti-IgE therapy, is an option for refractory cases, though its effectiveness is limited, especially in type IIb autoimmune CSU. This subtype is driven by IgG autoantibodies that activate mast cells and is often resistant to standard treatments.
The RILECSU phase 2 clinical trial has introduced a potential new option: rilzabrutinib, a next-generation, oral Bruton tyrosine kinase inhibitor (BTKI). Rilzabrutinib, taken at 1200 mg per day, demonstrated rapid and meaningful improvements in hives, itch, and angioedema symptoms within the 12-week double-blind treatment period. Its effect was observed across different CSU subtypes, including the more challenging type IIb.
Importantly, rilzabrutinib also led to reductions in biomarkers linked to disease activity, such as IgG anti-FcεRI, IL-31, and sMRGPRX2 – key indicators of severe CSU. Unlike earlier BTKIs, rilzabrutinib is both reversible and covalent in its binding, allowing high selectivity and minimal off-target effects. This design may explain its favourable safety profile; few adverse events were reported, and most were mild or moderate in nature.
This study positions rilzabrutinib as a promising therapy for CSU, especially in patients who do not respond to current treatments. Its ability to address both type I and type IIb CSU, coupled with a strong safety profile, offers hope for more personalised and effective management of this burdensome disease. Further trials will be essential to confirm these findings and support regulatory approval.
Reference
Giménez-Arnau A et al. Rilzabrutinib in antihistamine-refractory chronic spontaneous urticaria: the RILECSU Phase 2 randomized clinical trial. JAMA Dermatol. 2025;DOI:10.1001/jamadermatol.2025.0733.
