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Pretreatment with Ibrutinib, a Bruton's Tyrosine Kinase Inhibitor, Reduces Passive Systemic Anaphylaxis in a Murine Model
Saturday, March 5, 2016
South Exhibit Hall H (Convention Center)
Jennifer A. Regan, MD, PhD, Rebecca Krier-Burris, MS, Jeremy O'Sullivan, PhD, Paul Bryce, PhD, Bruce S. Bochner, MD FAAAAI
Rationale: There is an unmet need for therapeutics able to prevent serious allergic reactions including food allergy and anaphylaxis.  Bruton’s tyrosine kinase (Btk) has been shown to be critical for allergen reactivity in mast cells and basophils by transducing high affinity IgE receptor crosslinking signals into cellular activation and mediator release.  We sought to determine the effect of ibrutinib, an FDA-approved, irreversible Btk inhibitor for B cell malignancies, on systemic anaphylaxis using a murine model.

Methods: Anaphylaxis was induced in BALB/c mice using an established model for passive systemic anaphylaxis.   In brief, mice were sensitized by intravenous injection of 50 µg of ovalbumin (OVA)-specific IgE, then 24 hours later challenged by systemic administration of 50 µg OVA.  To test the effect of ibrutinib, mice were pretreated with 12.5 mg/kg ibrutinib or vehicle control via gastric gavage either as a single treatment (3 hours) or two treatments (23 and 3 hours) prior to OVA challenge. 

 

Results:  Pretreatment with ibrutinib compared to vehicle control inhibited passive systemic anaphylaxis as determined by a reduction of drop in body temperature and an improvement in clinical scores.  Inhibition was observed with both the single and dual ibrutinib pretreatment regimens.

 

Conclusions: These findings suggest that ibrutinib inhibits systemic anaphylaxis in a murine model.  Blockade of the Btk pathway may represent an achievable and clinically relevant therapeutic approach for prevention of anaphylaxis.