Leveraging BTKi in CSU Management

Bruton tyrosine kinase (BTK) acts as a critical signal transducer in the mast cell degranulation pathway, making it an attractive therapeutic target for chronic spontaneous urticaria (CSU). By blocking BTK, agents such as remibrutinib prevent downstream mast cell activation and subsequent release of histamine and other pro-inflammatory mediators involved in urticaria pathogenesis. This targeted approach allows for suppression of disease activity compared to antihistamines, which impact only a single mediator.

The REMIX 1 and REMIX 2 studies evaluated oral remibrutinib versus placebo in patients with moderate-to-severe CSU. These pivotal phase 3 trials enrolled almost 1000 participants and demonstrated significant improvements in urticaria activity scores and symptom control among those treated with remibrutinib. In addition, remibrutinib’s efficacy extended even to high-need patient subpopulations, including those with previous inadequate response to established biologic therapy.

BTK inhibitors are now poised to occupy a key position within the evolving CSU treatment paradigm. Their oral route, rapid onset, and robust efficacy and safety data make remibrutinib not only a viable alternative for refractory patients but also an option that can be considered earlier in the treatment algorithm. Shared decision-making based on patient history, preferences, and comorbidities will continue to shape the use of BTKi in CSU management, as recommended by emerging guideline updates.