Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge

Background: Omalizumab treatment suppresses Fcε{lunate}RI expression faster on blood basophils than skin mast cells. Objective: We used omalizumab to elucidate the relative contributions of basophil versus mast cell Fcε{lunate}RI activation in a nasal allergen challenge (NAC) model. Methods: Eighteen subjects with cat allergy were enrolled in a 3.5-month, double-blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing. At baseline, subjects underwent NAC with lavage for prostaglandin D₂ measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/Fcε{lunate}RI measurements. Basophil studies were repeated at day 3 and then weekly until cat allergen-induced BHR was <20% of baseline or until day 45. Baseline visit procedures were repeated after the BHR reduction (midstudy NAC) and at the treatment period's completion (final NAC). Results: Subjects treated with omalizumab who completed all NACs (n = 12) demonstrated significant mean reduction in BHR to an optimal dose of cat allergen by midstudy NAC compared with baseline (74% decrease; P = .001). In addition, these subjects demonstrated significant decreases in mean combined nasal symptom scores (50% decrease; P = .007) and total sneeze counts (59% decrease; P = .01) by midstudy NAC relative to baseline NAC. In contrast, measures of mast cell response (SPTT and nasal lavage prostaglandin D₂) were only significantly reduced by the final NAC. Subjects on placebo (n = 4) did not experience a shift in basophil, NAC symptom, or mast cell measures. Conclusion: Reduction in nasal symptom scores occurred when the basophil, but not mast cell, response was reduced on omalizumab, implicating a role for basophils in the acute NAC response.