Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma

doi:10.1067/mai.2003.49

Journal of Allergy and Clinical Immunology

Volume 111, Issue 1, January 2003, Pages 87-90

https://doi.org/10.1067/mai.2003.49 Get rights and content

Abstract

Background: Prevention of serious asthma exacerbations is an important therapeutic goal in patients with asthma. Objective: The purpose of this study was to investigate the effect of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody, on the rate of serious exacerbations during long-term therapy. Methods: A pooled analysis was completed of 3 multicenter, randomized, double-blind, placebo-controlled phase III studies with omalizumab in adults/adolescents aged ≥12 years (n = 1071) and in children aged 6 to 12 years (n = 334) who required treatment with inhaled corticosteroids for allergic asthma. Rates of serious asthma exacerbations were computed and compared between omalizumab- and placebo-treated patients. Serious exacerbations were those leading to unscheduled outpatient visits, emergency room treatment, or hospitalization during 1 year of treatment. Results: In all, 767 patients were treated with omalizumab (at least 0.016 mg/kg/IgE [IU/mL], administered subcutaneously every 4 weeks). Another 638 patients were treated with placebo. The rate of unscheduled, asthma-related outpatient visits was lower for the omalizumab-treated patients than for the placebo-treated patients (rate ratio [95% CI], 0.60 [0.44, 0.81]; P < .01), as were asthma-related emergency room visits (rate ratio [95% CI], 0.47 [0.24, 1.01]; P = .05). Importantly, hospitalizations for asthma were markedly reduced in patients receiving omalizumab (rate ratio [95% CI], 0.08 [0.00, 0.25]; P < .01). Conclusion: Omalizumab reduces the rate of serious asthma exacerbations and the need for unscheduled outpatient visits, emergency room treatment, and hospitalization in patients with moderate-to-severe allergic asthma. (J Allergy Clin Immunol 2003;111:87-90.)

Section snippets

Study Design

The aim of the current analysis was to assess the effects of omalizumab on exacerbations of asthma and unscheduled outpatient visits, emergency room treatments, and hospitalizations. We performed a pooled analysis of results from 3 multicenter, randomized, double-blind, placebo-controlled phase III clinical trials of omalizumab (studies 008, 009, and 010).7, 9 Two studies conducted in adolescents (≥12 years old) and adults enrolled 1071 patients7, 9; the third study involved 334 children aged 6

Demographics

Overall, 767 patients were randomized to omalizumab and 638 patients to placebo. Patient demographics and baseline characteristics were comparable between the 2 groups in each study.7, 8, 9

Asthma exacerbations

As previously reported, significantly fewer omalizumab-treated patients experienced asthma exacerbations (protocol-defined as worsening of asthma control requiring treatment with oral or intravenous corticosteroids or a doubling of the baseline dosage of inhaled corticosteroid). This difference was especially

Discussion

These findings show that omalizumab reduced the incidence rate of serious asthma exacerbations in adults/adolescents and children with allergic asthma requiring treatment with inhaled corticosteroids. The results extend previously reported findings showing that omalizumab reduces the frequency and incidence of asthma exacerbations while reducing the intake of inhaled corticosteroids in patients with allergic asthma.7, 8, 9

Reducing the incidence of serious asthma exacerbations has important

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Real-World Effectiveness of Omalizumab in Severe Allergic Asthma: A Meta-Analysis of Observational Studies
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Assessment of clinical outcomes in the real-world corroborates findings from randomized controlled trials (RCTs).
This meta-analysis evaluated real-world data of omalizumab on treatment response, lung function, exacerbations, oral corticosteroid (OCS) use, patient-reported outcomes (PROs), health care resource utilization (HCRU), and school/work absenteeism at 4, 6, and 12 months after treatment.
Observational studies in patients with severe allergic asthma (≥6 years) treated with omalizumab for ≥16 weeks, published from January 2005 to October 2018, were retrieved from PubMed, Embase, and Cochrane. A random-effects model was used to assess heterogeneity.
In total, 86 publications were included. Global evaluation of treatment effectiveness (GETE) was good/excellent in 77% patients at 16 weeks (risk difference: 0.77; 95% confidence interval [CI]: 0.70-0.84; I² = 96%) and in 82% patients at 12 months (0.82, 0.73-0.91; 97%). The mean improvement in forced expiratory volume in 1 second was 160, 220, and 250 mL at 16 weeks, 6 months, and 12 months, respectively. There was a decrease in Asthma Control Questionnaire score at 16 weeks (−1.14), 6 months (−1.56), and 12 months (−1.13) after omalizumab therapy. Omalizumab significantly reduced annualized rate of severe exacerbations (risk ratio [RR]: 0.41, 95% CI: 0.30-0.56; I² = 96%), proportion of patients receiving OCS (RR: 0.59, 95% CI: 0.47-0.75; I² = 96%), and number of unscheduled physician visits (mean difference: −2.34, 95% CI: −3.54 to −1.13; I² = 98%) at 12 months versus baseline.
The consistent improvements in GETE, lung function, and PROs, and reductions in asthma exacerbations, OCS use, and HCRU with add-on omalizumab in real-life confirm and complement the efficacy data of RCTs.
The impact of socioeconomic risk factors and mental health on asthma
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Cost-Effectiveness of Biologics for Allergic Diseases
2021, Journal of Allergy and Clinical Immunology: In Practice
The introduction of specific humanized monoclonal antibodies over the past 20 years has dramatically changed the treatment of allergic diseases. At present, 5 mAbs are licensed for treating moderate to severe allergic and eosinophilic asthma, atopic dermatitis, chronic spontaneous urticaria, chronic sinusitis with nasal polyps, and eosinophilic granulomatosis with polyangiitis. Given the high costs of biologics, understanding their cost-effectiveness is critical. As new biologics are developed and new indications are approved for existing biologics, the use of biologics for allergic diseases will increase. Conducting cost-effectiveness evaluations in parallel to efficacy and effectiveness trials will help patients, providers, payers, and policymakers in decision making.
Omalizumab Is an Effective Intervention in Severe Asthma with Fungal Sensitization
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Citation Excerpt :
In binding to IgE at the same site as the high-affinity FcεRI receptor, omalizumab selectively blockades the IgE-dependent allergic response.8 A meta-analysis of the data from 3 studies demonstrated that the addition of omalizumab to subjects with moderate to severe asthma reduced exacerbations and improved asthma symptoms.9 Omalizumab then would appear to be a rational choice in the treatment of either ABPA or SAFS, with the strong association between an IgE-mediated response to Aspergillus, associated with worsened asthma and progressive lung damage.
Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are important complications of severe asthma. The evidence for treating them with omalizumab is limited.
To determine the effectiveness of treatment with omalizumab in patients with severe allergic asthma comparing those with and without evidence of fungal sensitization using data recorded in the Australian Xolair Registry.
Data from 205 patients who received omalizumab and recorded in the Australian Xolair Registry were analyzed to determine change in the Juniper 5-item Asthma Control Questionnaire (ACQ-5) score, exacerbation frequency, and oral corticosteroid dose over a 24-month period of omalizumab treatment. Patients were grouped into cohorts on the basis of fungal sensitization, and an analysis of improvement in outcomes between baseline and 24 months was conducted within each group. A further subgroup analysis of patients with ABPA was also conducted.
Patients with SAFS (n = 62), including those with ABPA (ASAFS), were as likely to demonstrate significant improvements in ACQ-5 score and exacerbations and reduced regular oral corticosteroid dose over 24 months as those with severe asthma without sensitization to fungi (n = 156). After adjusting for age, sex, body mass index, smoking history, and baseline FEV₁%, the effects still remained. A subgroup analysis of 11 patients with ABPA similarly demonstrated a significant improvement on omalizumab.
Omalizumab is an effective therapy in ASAFS, leading to sustained improvements in symptoms and exacerbations for 24 months. The benefit for ABPA is less clear because of the small sample size.
Rapid desensitization of humanized mice with anti-human FcεRIα monoclonal antibodies
2020, Journal of Allergy and Clinical Immunology
Anaphylaxis is classically mediated by allergen cross-linking of IgE bound to the α chain of FcεRI, the mast cell/basophil high affinity IgE receptor. Allergen cross-linking of the IgE/FcεRI complex activates these cells, inducing release of disease-causing mediators, cytokines, and enzymes. We previously demonstrated that IgE-mediated anaphylaxis could be safely prevented in wild-type BALB/c mice by rapid desensitization with anti-mouse FcεRIα mAb.
This study sought to use humanized mice to extend these results to humans.
We actively immunized huFcεRIα/F709 mice, which express human (hu) instead of mouse FcεRIα and a mutant IL-4 receptor that lacks inhibitory function. We passively immunized huFcεRIα mice, as well as human cord blood–reconstituted reNSGS mice, which are immune-deficient, produce mast cell–stimulating human cytokines, and develop numerous human mast cells. For desensitization, we used anti-huFcεRIα mAbs that bind FcεRIα regardless of its association with IgE (noncompeting mAbs), and/or mAbs that compete with IgE for huFcεRIα binding (competing mAbs). Anaphylaxis was induced by intravenous injection of antigen or anti-huIgE mAb.
Anti-huFcεRIα mAb rapid desensitization was safer and more effective than allergen rapid desensitization and suppressed anaphylaxis more rapidly than omalizumab or ligelizumab. Rapid desensitization of naïve, IgE-sensitized huFcεRIα mice and huFcεRIα/F709 mice that were egg-allergic with anti-FcεRIα mAbs safely removed >98% of IgE from peritoneal mast cells and completely suppressed IgE-mediated anaphylaxis. Rapid desensitization of reNSGS mice with anti-FcεRIα mAbs also safely removed ∼98% of mast cell IgE and prevented IgE-mediated anaphylaxis.
Rapid desensitization with anti-FcεRIα mAbs may be a safe, effective, and practical way to prevent IgE-mediated anaphylaxis.

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^☆: Supported in part by Novartis Pharma AG, Basel, Switzerland, and Genentech, Inc, South San Francisco, Calif.

^☆☆: Reprint requests: Jonathan Corren, MD, Allergy Research Foundation, Inc, 1160 Wilshire Blvd, Suite 200, Los Angeles, CA 90025.

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Asthma, Rhinitis, Other Respiratory Diseases: Brief CommunicationOmalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma☆,☆☆

Abstract

Section snippets

Study Design

Demographics

Asthma exacerbations

Discussion

J Allergy Clin Immunol

Global strategy for asthma management and prevention

An economic evaluation of asthma in the United States

N Engl J Med

A national estimate of the economic costs of asthma

Am J Respir Crit Care Med

Asthma

JAMA

Anti-IgE as novel therapy for the treatment of asthma

Curr Opin Pulmon Med

Omalizumab

Drugs

Asthma, Rhinitis, Other Respiratory Diseases: Brief Communication
Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma☆,☆☆