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Previous Volume 341:1966-1973 December 23, 1999 Number 26 Next

	Full Text PDF Editorial by Barnes, P. J. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Immune responses mediated by IgE are important in the pathogenesis of allergic asthma. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE and blocks its interaction with mast cells 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 (age 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 µg per kilogram of body weight per nanogram of IgE per milliliter) or low-dose rhuMAb-E25 (2.5 µg per kilogram per nanogram 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 weeks. For the first 12 weeks of the study, the subjects continued the regimen of corticosteroids they had received before enrollment. During the following eight weeks, the doses of corticosteroids were tapered in an effort to discontinue this therapy. The primary outcome measure was an improvement in the 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 symptoms.

Results A total of 106 subjects were assigned to receive a high dose of rhuMAb-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. After 12 weeks of therapy, the mean (±SE) scores were 2.8±0.1 in the high-dose group (P=0.008) and 2.8±0.1 in the low-dose group (P=0.005), as compared 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 corticosteroids than in the placebo group, but only some of the differences were 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 IgE has potential as a treatment for subjects with moderate or severe allergic asthma.

Source Information

From the Departments of Pediatrics and Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver (H.M.); Genentech, South San Francisco, Calif. (R.B.F., J.Q.S., J.D.R., M.L.W.); the Department of Medicine, University of Wisconsin Medical School, Madison (R.K.B.); and the Department of Medicine, East Carolina University, Greenville, N.C. (W.J.M.).

Address reprint requests to Dr. Metzger at the Section of Allergy/Immunology, Department of Medicine, East Carolina University School of Medicine, Greenville, NC 27858.

Full Text of this Article

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Treatment of Allergic Asthma with Monoclonal Anti-IgE Antibody
Salvi S. S., Babu K. S., Milgrom H., Fick R. B., Metzger W. J.
Extract | Full Text  
N Engl J Med 2000; 342:1292-1293, Apr 27, 2000. Correspondence

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