Treatment of allergic asthma with monoclonal anti-IgE antibody

Background: Immune responses mediated by IgE are important in the pathogene sis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb -E25) forms complexes with free IgE and blocks its interaction with mast ce lls and basophils. We studied the efficacy of rhuMAb-E25 as a treatment for moderate-to-severe allergic asthma. Methods: After a 4-week run-in period, we randomly assigned 317 subjects (a ge range, 11 to 50 years) who required inhaled or oral corticosteroids (or both) to receive either placebo or one of two regimens of rhuMAb-E25: high- dose rhuMAb-E25 (5.8 microg per kilogram of body weight per nanogram of IgE per milliliter) or low-dose rhuMAb-E25 (2.5 microg per kilogram per nanogr am of IgE per milliliter) intravenously on days 0 (half a dose), 4 (half a dose), and 7 (full dose) and then once every 2 weeks thereafter for 20 week s. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the followin g eight weeks, the doses of corticosteroids were tapered in an effort to di scontinue this therapy. The primary outcome measure was an improvement in t he asthma symptom score at 12 weeks, according to a 7-point scale, in which a score of 1 indicated no symptoms and a score of 7 the most severe sympto ms. Results: A total of 106 subjects were assigned to receive a high dose of rh uMAb-E25, 106 were assigned to receive a low dose, and 105 were assigned to receive placebo. At base line, the mean asthma symptom score was 4.0. Afte r 12 weeks of therapy, the mean (+/-SE) scores were 2.8+/-0.1 in the high-d ose group (P=0.008) and 2.8+/-0.1 in the low-dose group (P=0.005), as compa red with 3.1+/-0.1 in the placebo group. At 20 weeks, the mean scores were 2.7+/-0.1 in both the high-dose group (P=0.048) and the low-dose group (P=0 .14), as compared with 2.9+/-0.1 in the placebo group. More subjects in the two rhuMAb-E25 groups were able to decrease or discontinue their use of co rticosteroids than in the placebo group, but only some of the differences w ere significant. After 20 weeks, serum free IgE concentrations decreased by a mean of more than 95 percent in both rhuMAb-E25 groups. The therapy was well tolerated. After 20 weeks, none of the subjects had antibodies against rhuMAb-E25. Conclusions: A recombinant humanized monoclonal antibody directed against I gE has potential as a treatment for subjects with moderate or severe allerg ic asthma. (N Engl J Med 1999;341:1966-73.) (C)1999, Massachusetts Medical Society.