The correct answer is D. Remibrutinib.

Remibrutinib is an oral Bruton’s tyrosine kinase (BTK) inhibitor under development for the treatment of chronic spontaneous urticaria (CSU). Results from Phase III trials are promising, demonstrating sustained efficacy and a favorable safety profile over 52 weeks. FDA approval could be anticipated in 2025.

The BTK is crucial for mast cell activation in CSU. When an allergen cross-links IgE bound to FcεRI, it triggers phosphorylation of ITAMs, leading to activation of Syk kinase, which in turn activates BTK. BTK activation leads to mast cell degranulation.  Remibrutinib blocks BTK, preventing mast cell activation and reducing urticaria symptoms.

Most/all BTK inhibitors end in -nib and contain –brutin somewhere in their name!  Most are used for hematologic malignancies and/or autoimmune diseases, as BTK is heavily involved in survival and proliferation of B cells, however BTK inhibitors are increasingly being studied in the use of asthma and allergy.

Incorrect answers:

Dupilumab
Dupilumab is a human monoclonal antibody that targets interleukin-4 receptor alpha (IL-4Rα), inhibiting the signaling of both IL-4 and IL-13 cytokines.

Benralizumab
Benralizumab is a monoclonal antibody that binds to the interleukin-5 receptor alpha (IL-5Rα) on eosinophils and basophils.

Cromolyn sodium
Cromolyn sodium is a mast cell stabilizer that prevents the release of histamine and other inflammatory mediators by binding to mast cell membranes.

Omalizumab
Omalizumab is a monoclonal antibody that binds to free immunoglobulin E (IgE) in the blood, preventing IgE from attaching to its receptors on mast cells and basophils.

References:

Kolkhir P, Bonnekoh H, Metz M, Maurer M. Chronic Spontaneous Urticaria: A Review. JAMA. 2024 Nov 5;332(17):1464-1477. doi: 10.1001/jama.2024.15568. PMID: 39325444., Kolkhir P, Fok JS, Kocatürk E, Li PH, Okas TL, Marcelino J, Metz M. Update on the Treatment of Chronic Spontaneous Urticaria. Drugs. 2025 Mar 12. doi: 10.1007/s40265-025-02170-4. Epub ahead of print. PMID: 40074986., Clore L, Tillinghast W, Jain V, et al. Remibrutinib reduces CSU symptoms and rescue medication use in patients with chronic spontaneous urticaria despite absence of background medication. J Am Acad Dermatol. 2024;91(3):AB81.

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