911:
Administration of two doses of an oral, irreversible inhibitor of Bruton’s tyrosine kinase (BTK) to food allergic adults abrogates skin test responses and eliminates IgE-mediated basophil activation ex vivo.
Monday, March 5, 2018: 2:15 PM
S330GH (Convention Center)
Melanie C. Dispenza, MD PhD, , ,
RATIONALE: There is an unmet need for therapies capable of preventing anaphylaxis. BTK is an enzyme that is required for FcεRI signaling in mast cells and basophils; therefore, BTK inhibitors such as ibrutinib have the potential to prevent anaphylaxis. We hypothesized that short-term ibrutinib use would reduce allergic responses in food allergic subjects.

METHODS: Six adults with a history of IgE-mediated allergy to peanut and/or tree nuts were enrolled. After screening, subjects were given ibrutinib 420 mg daily for 2 to 7 days. Skin prick tests (SPTs) to relevant foods and basophil activation testing (BAT) were performed at baseline, during ibrutinib treatment, and after cessation of therapy.

RESULTS: Two days of ibrutinib treatment significantly reduced SPT wheal and flare area (77 and 86% reductions, respectively; p<0.0001, n=25). Overall, 44% of all skin tests became negative (wheal < 3mm diameter). Additional doses of ibrutinib for 4 or 7 days maintained significantly reduced SPTs, but did not demonstrate additional suppression compared to 2 days. Histamine control SPTs were unaffected. Anti-IgE induced (but not fMLP-induced) BAT was completely negative after 2 doses (p=0.0002) and remained negative at 4 and 7 days. Finally, the majority of SPTs and BAT returned to baseline levels 1 week after cessation of therapy. No clinical or serologic toxicity from ibrutinib treatment was observed.

CONCLUSIONS: Short-term ibrutinib therapy (as few as 2 doses) eliminates or drastically reduces SPT responses to foods in allergic subjects, and completely abolishes IgE-mediated BAT. Ibrutinib could potentially be used to prevent allergic responses including anaphylaxis.