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A phase II study of Bruton’s tyrosine kinase inhibition for the prevention of anaphylaxis

ARTICLE: A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis

AUTHORS: Ragha V Suresh, Collin Dunnam, Dhananjay Vaidya, Robert A Wood, Bruce S Bochner, Donald W MacGlashan JrMelanie C Dispenza

JOURNAL: J Clin Invest. 2023 Aug 15;133(16):e172335. doi: 10.1172/JCI172335


Background: IgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy.

Methods: After undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut protein to elicit an objective clinical reaction.

Results: At baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range 444-4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious.

Conclusion: Acalabrutinib pretreatment achieved clinically relevant increases in patients' tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials.

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Kelsey Bennett