Original Articles: Mechanisms of Allergy
Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma,☆☆

https://doi.org/10.1067/mai.2001.117880Get rights and content

Abstract

Background: A recombinant humanized anti-IgE mAb, omalizumab, forms complexes with free IgE, blocking its interaction with mast cells and basophils; as a consequence, it might be effective in the treatment of asthma. Objective: The purpose of this study was to evaluate the efficacy and safety of omalizumab in the treatment of inhaled corticosteroid–dependent asthma. Methods: In this phase III, double-blinded, placebo-controlled trial, 525 subjects with severe allergic asthma requiring daily inhaled corticosteroids were randomized to receive placebo or omalizumab subcutaneously every 2 or 4 weeks, depending on baseline IgE level and body weight. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment and tapered during a further 12-week treatment period. Results: Omalizumab treatment resulted in significantly fewer asthma exacerbations per subject and in lower percentages of subjects experiencing an exacerbation than placebo treatment during the stable steroid phase (0.28 vs 0.54 [P = .006] and 14.6% vs 23.3% [P = .009], respectively) and during the steroid reduction phase (0.39 vs 0.66 [P = .003] and 21.3% vs 32.3% [P = .004], respectively). Beclomethasone dipropionate reduction was significantly greater with omalizumab treatment than with placebo (median 75% vs 50% [P < .001]), and beclomethasone dipropionate discontinuation was more likely with omalizumab (39.6% vs 19.1% [P < .001]). Improvements in asthma symptoms and pulmonary function occurred along with a reduction in rescue β-agonist use. Omalizumab was well tolerated, with an adverse-events profile similar to that of placebo. Conclusion: The addition of omalizumab to standard asthma therapy reduces asthma exacerbations and decreases inhaled corticosteroid and rescue medication use. (J Allergy Clin Immunol 2001;108:184-90.)

Section snippets

Subjects

Male or female allergic asthmatics aged 12 to 75 years who were symptomatic despite treatment with ICSs were eligible if they met the following criteria: duration of asthma, ≥1 year; positive immediate responses on skin prick testing to at least 1 common allergen, including Dermatophagoides farinae , Dermatophagoides pteronyssinus , cockroach (whole body), dog, or cat; total serum IgE ≥30 IU/mL to ≤700 IU/mL; FEV1 reversibility of ≥12% within 30 minutes after administration of albuterol (90-180

Demographics

With respect to demographic characteristics, the 2 groups were not statistically different (Table I).

. Baseline demographic characteristics of intent-to-treat population

Empty CellOmalizumab (n = 268)Placebo (n = 257)
Sex (no. of subjects [%])
 Male104 (38.8)111 (43.2)
 Female164 (61.2)146 (56.8)
Race (no. of subjects [%])
 Caucasian238 (88.8)229 (89.1)
 Black21 (7.8)16 (6.2)
 Other9 (3.4)12 (4.7)
Age (mean [range]) (y)39.3 (12-73)39.0 (12-74)
Age group (no. of subjects [%])
 12-17 y20 (7.5)21 (8.2)
 18-64 y241 (89.9)229

Discussion

Allergic asthmatic patients enrolled in this study were not well controlled before randomization while being treated with a significant dose of BDP (400-800 μg per day). This, in conjunction with a long history of asthma, low FEV1 on entry into the study, or significant symptoms as judged from daily diary card recordings, classified 99.3% of these patients as severe persistent asthmatics. In this often problematic patient population, omalizumab therapy was associated with significantly fewer

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Supported by a grant from Novartis Pharmaceuticals Corporation and Genentech, Inc.

☆☆

Reprint requests: William Busse, MD, Department of Medicine, Section of Allergy and Clinical Immunology, University of Wisconsin Hospital & Clinics, Madison, WI 53792.

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