USE OF AN ANTI-IGE HUMANIZED MONOCLONAL-ANTIBODY IN RAGWEED-INDUCED ALLERGIC RHINITIS

Background: Increased serum levels of antigen-specific IgE are often a ssociated with allergic respiratory disorders. RhuMAb-E25, a recombina nt humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. Objective: We hy pothesized that rhuMAb-E25 would decrease total serum IgE and reduce s ymptoms. Methods: Two hundred forty subjects were enrolled into five g roups to determine the safety, tolerance, and efficacy of repeated adm inistration of rhuMAb-E25 in adults with ragweed-induced allergic rhin itis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by admin istration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutane ously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intra venous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. Results: Adverse events were mild, and no differences were observed i n the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores, RhuMAb-E2 5 decreased serum free IgE levels in a dose- and baseline IgE-dependen t fashion. However, only 11 subjects had IgE levels that were suppress ed to undetectable levels (less than or equal to 24 ng/ml), a sample t oo small to demonstrate significant differences and clinical efficacy, Thus the case for efficacy was not proven. Nonetheless, the study con firms that it is safe to repeatedly administer rhuMAb-E25 over a perio d of months. Conclusions: Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in ade quate doses, rhuMAb-E25 should be an effective therapy for allergic di seases.