| Message: NCBINCBI Logo
Skip to main content
Skip to navigation
Resources
How To
About NCBI Accesskeys
PMC
US National Library of Medicine
National Institutes of Health
Search database
PMC
Search term
Search
Advanced Journal listHelp
COVID-19 Information
Public health information (CDC)Research information (NIH)SARS-CoV-2 data (NCBI)Prevention and treatment information (HHS)Español
Try out PMC Labs and tell us what you think. Learn More.
Journal ListTher Clin Risk Managv.3(4); 2007 AugPMC2374942
Logo of tcriskman
Ther Clin Risk Manag. 2007 Aug; 3(4): 613–619.
Published online 2007 Aug.
PMCID: PMC2374942
PMID: 18472983
A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma
Gennaro D'Amato, Antonello Salzillo, Amedeo Piccolo, Maria D'Amato, and Gennaro Liccardi
Author information Copyright and License information Disclaimer
Division of Respiratory and Allergic Diseases, High Speciality Hospital "A.Cardarelli", Napoli, Italy
Correspondence: Prof Gennaro D'Amato Director, Division of Respiratory and Allergic Diseases, High Speciality Hospital "A.Cardarelli", Rione Sirignano, 10–80121 Napoli, Italy Email ti.tfosibuq@otamadg
This article has been cited by other articles in PMC.
Go to:
Abstract
Bronchial asthma is recognized as a highly prevalent health problem in the developed and developing world with significant social and economic consequences. Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs. The pathogenetic background of allergic-atopic bronchial asthma is characterized by airway inflammation with infiltration of several cells (mast cells, basophils, eosinophils, monocytes, and T-helper (Th)2 lymphocytes). However, in atopic asthma the trigger factors for acute attacks and chronic worsening of bronchial inflammation are aeroallergens released by pollens, dermatophagoides, and pets, which are able to induce an immune response by interaction with IgE antibodies. Currently anti-inflammatory treatments are effective for most asthma patients, but there are asthmatic subjects whose disease is not completely controlled by inhaled or systemic corticosteroids and who account for a signific ant portion of the healthcare costs of asthma. A novel therapeutic approach to asthma and other allergic respiratory diseases involves interference in the action of IgE, and this antibody has been viewed as a target for novel immunological drug development in asthma. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody approved for treatment of moderate to severe IgE-mediated (allergic) asthma. This non-anaphylactogenic anti-IgE antibody inhibits IgE functions, blocking free serum IgE and inhibiting their binding to cellular receptors. By reducing serum IgE levels and IgE receptor expression on inflammatory cells in the context of allergic cascade, omalizumab represents a new class of mast cells stabilizing drugs; it is a novel approach to the treatment of atopic asthma. Omalizumab therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids. Moreover, omalizu mab improves quality of life of patients with severe persistent allergic asthma which is inadequately controlled by currently available asthma medications. In conclusion omalizumab may fulfil an important need in patients with moderate to severe asthma.
Keywords: airway hyper-reactivity, asthma, allergic respiratory diseases, atopic respiratory diseases, anti-IgE therapy, hypersensitivity, monoclonal anti-IgE antibody, omalizumab
Go to:
Introduction
Bronchial asthma is a chronic disease of airways which is recognized as a highly prevalent health problem in the developed and developing world. Asthma is characterized by bronchial inflammation, airway hyper-responsiveness induced by specific and nonspecific stimuli, and reversible bronchial obstruction with the appearance of respiratory symptoms such as dyspnea, chest tightness, wheezing, and cough. Airway inflammation plays a central role in the pathogenesis of bronchial asthma and is associated with an increase in airway responsiveness to several trigger factors such as aeroallergens which induce bronchoconstriction in atopic asthma patients.
The pathogenesis of bronchial asthma is not completely understood and it is well known that this clinical condition has a multifactorial etiology (D'Amato and Holgate 2002; Loddenkemper et al 2003; Masoli et al 2004; Rabe et al 2004). Although some asthmatic subjects exhibit a pathogenesis in which immunoglobulin E (IgE)-mediated mechanisms are not evident, asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis (Holt et al 1999). Allergic bronchial asthma is a Th2 mediated chronic inflammatory disease of the airways, and IgE antibodies, Th2 derived cytokines, and eosinophils play a major role in the development of chronic airway inflammation, which is observed even in subjects with very mild disease (Wenzel et al 1991; Busse et al 1995; Novak and Bieber 2003). In other words the development of inflammation in asthma involves a complex array of several inflammatory mediators that promote the recruitment and activation of various different immune cells (T-lymphocytes of the T-helper type 2 phenotype, eosinophils, macrophages/monocytes, and mast cells) and regulate inflammatory cell trafficking into the lungs.
Activation of chemokine receptors triggers multiple cascades of intracellular signaling events that lead to recruitment and activation of immune effector cells. The inhibition of specific chemokines and receptors could prevent the excessive recruitment of inflammatory cells into the airways.
A number of selective chemokine receptor antagonists or anti-inflammatory chemokines are currently at various stages of development, but there are no products yet ready for clinical use.
Go to:
From IgE antibodies to therapy with monoclonal anti-IgE (omalizumab)
Elevated serum levels of specific IgE in response to common environmental aeroallergens are a key component in the pathogenesis of allergic asthma. IgE antibodies cause chronic airway inflammation through effector cells such as mast cells and basophils activated via high-affinity (FcεRI) or low-affinity (FcεRI) IgE receptors which bind these antibodies.
IgE is an immunoglobulin, consisting, like the other four antibody classes, of a variable antigen-binding fragment (Fab) region and a receptor-binding constant (Fc) region. The whole molecule consists of two heavy (H) ε chains and two light (L) chains of the k or λ type.
There is also high association between serum IgE levels and FcεRI receptors on precursor dendritic cells, and the expression of these receptors on antigen presenting cells such as dendritic cells is increased in asthmatic patients (Hollowaj 2001).
Since the discovery of IgE this antibody has been viewed as a target for novel immunological drug development in asthma, and a number of strategies to inhibit its proinflammatory action have been developed.
Current treatment for asthma suggested by the Global Initiative for Asthma (GINA) guidelines includes several drugs (relievers and controllers), in particular corticosteroids able to reduce recruitment and activation of inflammatory cells, in particular eosinophils, in the airways (NHLBI -GINA 2006).
Previous GINA documents subdivided asthma into four categories by severity based on the level of symptoms, airflow limitation, and lung function variability: Intermittent, Mild Persistent, Moderate Persistent, or Severe Persistent.
The GINA 2006 update recognizes, however, that asthma severity involves both the severity of the underlying disease and its responsiveness to treatment. In addition, severity is not an unvarying feature of an individual patient's asthma, but may change over months or years. Therefore GINA, for this purpose, suggests that a periodic assessment of asthma control is more relevant and useful.
The burden of asthma is greatest in patients with inadequately controlled severe persistent asthma symptoms, limitations in normal daily activities, medical resource utilization, and both direct and indirect costs.
The available treatments are effective for most of these asthma patients, but there are subjects affected by severe asthma who continue to experience debilitating disease, because their control is incomplete by inhaled or systemic corticosteroids associated with other drugs such as beta-2 bronchodilators (short- and long-acting), leukotriene receptor antagonists (Bateman 2004; Partridge 2006).
These patients are at high risk of life-threatening exacerbation, hospitalization, and mortality (Tough 1998; Serra-Batles et al 1998; Guite 1999) and are most affected in terms of quality of life (Turk 2005).
The economic impact of asthma is considerable. Approximately US$13 billion were spent in the United States in 1998 (for indirect and direct cost) (Redd 2002) and €18 billion in Europe in 2003 (European Lung white book 2003).
Several studies have also indicated that asthma severity is associated not only with poor control, such as symptoms, recurrent hospitalization, lower quality of life (QoL), but also with higher social costs (Strunk and Bloomberg 2006), and that the economic burden of asthma increases with asthma severity and is greatest in this patient group (Antonicelli et al 2004).
Go to:
Omalizumab in the treatment of IgE-mediated (allergic) asthma
Omalizumab, an anti-IgE monoclonal antibody, can reduce free IgE levels avoiding the binding of IgE to FcεRI without the following development of allergic reaction (Boulet et al 1997; Fahy et al 1997; Chang 2000; Fahy 2000; Holgate et al 2001; Godard et al 2002; Kuehr et al 2002; Mankad et al 2003; D'Amato et al 2004, 2006). Omalizumab acts as a neutralizing antibody by binding IgE at the same site (Cε3 domain of Fc fragment) as the high affinity receptor (FcεRI) binds IgE. Consequently, IgE effector functions (cross linking IgE and triggering degranulation and synthesis of new-generated chemical mediators of IgE-sensitized cells) and the following activation of mast cells and basophils are inhibited (Buhl et al 2002a, b; Ayres et al 2004; Deniz and Gupta 2005; Holgate et al 2005) (Table 1). In other words in allergic subjects, and in the elderly (Milgrom et al 2001), omalizumab prevents the activation of cellular response and reduces occurrence of asthma symptoms (see Table 2).
Table 1
Biological characteristics of omalizumab
Omalizumab expresses a high degree of isotype specificity and can neutralize serum free IgE without affecting other antibody classes.
Omalizumab binds to serum free IgE and reduces IgE serum concentration, but does not bind to high- or low-affinity IgE receptors on inflammatory cells. However, it blocks IgE binding to these receptors and the IgE effector cells of inflammation are "disarmed".
Long-term treatment (3 months or more) with omalizumab induced down-regulation of the high-affinity receptors on basophils and dendritic cells.
Omalizumab does not induce extensive immune complex formation, but only microcomplexes (thrimeric or exameric) which are not able to induce immune-complex pathology.
Omalizumab activity does not depend on the allergic-atopic sensitization to various types of aeroallergens (seasonal and/or perennial).
Omalizumab is active in case of IgE-mediated sensitization to one or more aeroallergens.
Table 2
Omalizumab in clinical studies in allergic asthma patients
Omalizumab has been shown to:
Decrease IgE-induced bronchoconstriction during both the early- and late-phase responses to inhaled allergen during the bronchial provocation tests.
Reduce skin prick test response to allergenic extracts.
Reduce asthma exacerbations regardless of the type of seasonal or perennial allergic sensitization.
Have a corticosteroid sparing effect.
Reduce the use of bronchodilators.
Improve also the nasal symptoms in subjects with allergic rhinitis associated with asthma.
Improve quality of life in patients with asthma, and also in those with severe persistent allergic asthma that is inadequately controlled by currently available asthma medication.
Have a reassuring safety profile similar to that of placebo. In malignant neoplasms observed in patients treated with omalizumab, blinded and unblended expert oncologist review showed that the neoplasms were most likely pre-existent and there was no evidence that any of neoplasms were linked causally to omalizumab treatment.
Studies in patients with atopic asthma showed that anti-IgE antibodies decrease serum IgE levels in a dose-dependent manner and allergen-induced bronchoconstriction during both the early and late-phase responses to inhaled allergen (Chang 2000; Fahy 2000).
Serum free IgE is dramatically reduced after omalizumab administration and the expression of high-affinity receptors is significantly reduced after 3 months' treatment (MacGlashan et al 1997). Also, skin test reactivity is reduced by omalizumab (Togias et al 1998).
In patients who experience asthma associated with allergic rhinitis there is an improvement also in nasal symptoms (Casale et al 1999; Adelroth et al 2000; Kopp et al 2002; Plewako et al 2002; Vignola et al 2004). Omalizumab administered together with specific immunotherapy can help to reduce risk of serious adverse events such as anaphylaxis and the need for epinephrine and corticosteroid use to treat adverse reactions (Casale 2006). However, omalizumab is useful also if used without contemporaneous administration of specific immunotherapy.
In several clinical controlled trials omalizumab reduced asthma-related symptoms, decreased corticosteroid use, and improved quality of life of asthmatic patients (Buhl et al 2002a, b; Ayres et al 2004; Deniz and Gupta 2005; Niebauer et al 2006). Recent studies show the benefits of anti-IgE as add-on therapy in patients with moderate and severe persistent asthma who are inadequately controlled by antiasthma pharmacological therapy. The anti-IgE approach to asthma treatment has several advantages, including concomitant treatment of other IgE-mediated diseases (allergic conjunctivitis and rhinitis, atopic dermatitis, and food allergy) and a favorable side-effect profile regardless of the type of allergic sensitization (seasonal or perennial) (Casale et al 1999; Adelroth et al 2000; Buhl et al 2002b; Plewako et al 2002; Kopp et al 2002; Ayres et al 2004; Vignola et al 2004; Deniz and Gupta 2005). Omalizumab was shown not only to inhibit mast cell and basophil responses but also to have an inhibiting effect on inflammatory cells, such as eosinophils, T lymphocytes, and B lymphocytes which are fundamental to the chronic inflammatory response in allergic diseases such as asthma. This increased understanding places anti-IgE therapy firmly in the domain of an anti-inflammatory treatment for chronic allergic disease, with effect on multiple cell types (Chang and Shiung 2006; D'Amato 2006).
Severe or refractory asthma remains a frustrating disease for both patients and the clinicians treating them (Busse et al 2000; Humbert et al 2005; Wenzel 2005; Moore et al 2007).
Severe asthma has been defined as persisting symptoms due to asthma despite high-dose inhaled steroids (1000 μg beclometasone dipropionate or equivalent) plus long- acting beta-2 agonist (LABA), with the requirement for either maintenance systemic steroids or at least two rescue courses of steroids over 12 months and despite trials of add-ons such as leukotriene-receptor antagonist or theophylline.
The Global Initiative for Asthma (GINA) document for patients with uncontrolled asthma (step 5) recommends the use of high-dose inhaled corticosteroids plus a LABA, and, if required, one more additional controller such as omalizumab.
Response to treatment can take several weeks to appear and it is suggested that patients should be treated for at least 12 weeks before efficacy is assessed (Bousquet et al 2005).
Go to:
Experimental and controlled clinical studies
During the clinical trial on omalizumab 7 pivotal studies were performed on patients with moderate to severe IgE-mediated allergic asthma. One of these, the INNOVATE (INvestigatioN of Omalizumab in seVere Asthma TrEatment) study, was specifically designed to evaluate the efficacy and safety of add-on therapy with omalizumab in this difficult-to-treat asthma population (Humbert et al 2005).
In the INNOVATE trial were enrolled patients aged 12–75 years with severe persistent allergic asthma (GINA step 3 or 4 clinical features despite step 4 therapy). 108 centers in 14 countries participated in the study. Subjects enrolled had reduced lung function and not adequate symptom control despite therapy with a high dose of inhaled corticosteroids (ICS) (>1000 μg/day beclometasone dipropionate equivalent) and LABA stimulant bronchodilators, with a recent history of clinically significant exacerbation. After a run-in phase, patients were randomized to receive double-blind therapy with omalizumab or placebo for 28 weeks.
The primary efficacy variable was the rate of clinically significant asthma exacerbations (defined as a worsening of asthma symptoms requiring treatment with systemic corticosteroids). Other efficacy variables included the rate of severe exacerbations (peak expiratory flow (PEF) or forced expiratory volume in 1 second (FEV1) <60% of personal best, requiring treatment with systemic corticosteroids), total emergency visits for asthma, asthma-related quality of life (Juniper Adult Asthma Quality of Life Questionnaire; AQLQ), clinical symptom score, morning PEF, rescue medication use, and global evaluation of treatment effectiveness by patients and investigators. Safety was evaluated by observing adverse events and by monitoring laboratory parameters and vital signs. A total of 419 patients were included in the efficacy analyses (omalizumab, n = 209; placebo, n = 210). All patients were receiving ICS and LABA and two-thirds were receiving additional controller medications (including 22% oral corticosteroids). Patients had experienced an average of 2.1 exacerbations per year requiring systemic corticosteroids and 67% were considered at high risk of asthma-related death (based on previous history of emergency department or hospital visits or intubations).
After adjusting for an observed imbalance in asthma exacerbation history prior to randomization, the rate of clinically significant asthma exacerbations was significantly reduced by 26.2% with omalizumab versus placebo (0.68 and 0.91, respectively; p = 0.042).
Treatment with omalizumab significantly reduced the rate of severe asthma exacerbations in comparison with placebo (0.24 vs 0.48, p = 0.002) and the rate of total emergency visits for asthma (0.24 vs 0.43, p = 0.038). Significantly greater improvements were obtained with omalizumab compared with placebo in AQLQ scores, with a significantly greater proportion of patients receiving omalizumab achieving a clinically meaningful (>0.5-point) improvement from baseline compared with placebo treated patients (61% and 48%, respectively; p = 0.008).
The overall changes from baseline in mean morning PEF (p = 0.042) and total asthma symptom score (p = 0.039) during the treatment period were also significantly greater with omalizumab, which was considered more effective than placebo (p < 0.001) by both investigators and patients.
The pooled data from all clinical studies in patients with severe persistent asthma show that omalizumab is highly efficacious as add-on treatment to concomitant asthma therapy, as shown by the consistent reduction in asthma exacerbation rates compared with control-treated patients. Overall, exacerbations were significantly reduced (p < 0.0001) by 38.3% (annualized rate: 0.910 vs 1.474) with omalizumab compared with the control group (Table 3).
Table 3
Reduction in asthma exacerbation rates across studies
Rate per year P-Value for rate ratio Exac. rate treatment difference
Omalizumab Control
INNOVATE study 1.37 1.86 0.042 0.49
ETOPA study1 0.98 2.47 <0.001 1.49
SOLAR study2 0.49 0.79 0.027 0.29
Busse study3,4 0.59 0.99 <0.001 0.40
Solèr study5,6 0.51 1.21 <0.001 0.70
Holgate study7 1.18 1.60 0.165 0.42
ALTO safety study 1.02 1.20 0.077 0.18
Pooled 0.91 1.47 <0.001 0.56
1 Ayres et al 2004
2 Vignola et al 2004
3 Busse et al 2001
4Lanier et al 2003
5Solèr et al 2001
6 Buhl et al 2002
7Holgate et al 2004
Omalizumab significantly reduced the rate of emergency visits for asthma care by 47% compared with control therapy (p < 0.0001). Hospital admissions were reduced by 52%, emergency room visits by 61%, and unscheduled doctor visits by 47% (Bousquet 2005).
The clinical study showed also that side-effects following treatment with omalizumab were mild to moderate and did not differ significantly from placebo with the exception of injection site reactions, and no anti-omalizumab antibody response has been observed (Walker 2006).
A recent exploratory study on allergic subjects living in poor urban areas of Brazil, at high risk of helminthes infections, showed that omalizumab appeared to be effective and safe, but may be associated with a possible slightly increased risk of infections (not statistically significant) (Cruz 2007).
Further studies will need to focus on the utility of long-term treatment with anti-IgE to reduce the risk of life-threating reactions in subjects with food allergy, latex allergy, or stinging insect hypersensitivity.
Go to:
Preparation for use
Omalizumab is administered by subcutaneous injection. The appropriate dose and dosing frequency of omalizuamb is determined by baseline IgE (IU/mL) measured before start of treatment, and body weight (kg). Based on these measurements, 75–375 mg of omalizumab in 1–3 injections may be needed for each administration.
Omalizumab is supplied as a lyophilized, sterile powder in single-use, 5-mL vials designed to deliver either 150 or 75 mg on reconstitution with sterile water for injection. The powder requires 15–20 minutes or more to dissolve. The solution is viscous and must be carefully drawn up into the syringe before it is administered. Usually the injection needs 5–10 seconds for administration. Once prepared, omalizumab must be injected within 4 hours if at room temperature or 8 hours if refrigerated. It is important to schedule appointment for injection, avoiding preparing injection until the patient arrives. This results in visits that take 1 hour or more, since 30 minutes of observation after the injection are recommended.
Total serum IgE levels are generally increased during treatment, since there are circulating IgE-antiIgE complexes (Hamilton et al 2005).
Go to:
Conclusions
Studies of patients with allergic asthma show that anti-IgE treatment with omalizumab has a reassuring safety profile. The drug was approved for commercial use in allergic asthma by the Federal Drug Administration in June 2003 and by the European Agency for Evaluation of Medicinal Products in July 2005.
Analysis of data from controlled clinical trials carried with patients affected by severe allergic asthma showed that omalizumab is well-tolerated and safe both in short-term and long-term studies. It is well tolerated, and its overall adverse event profile is similar to that of placebo.
Several clinical studies have shown no evidence that omalizumab enhanced the risk of anaphylactic reactions, infections or parasitic infestations, or bleeding-related or any immune complex diseases or similar syndromes. As for malignant neoplasms observed in patients treated with omalizumab during a pivotal trial, blinded and unblended expert oncologists review showed that the neoplasms were most likely pre-existent and there was no evidence that any of neoplasms were linked causally to omalizumab treatment.
Because omalizumab is administered infrequently, with twice-monthly or monthly dosing, anti-IgE therapy may be useful in patients who have difficulty in complying with daily treatment.
Since omalizumab treatment induces a reduction in FcεRI and IgE+ cells in the airways of asthma patients and because a relationship between FcεRI expression and fatal asthma has been hypothesized (Fregonese et al 2004), the possible effect of omalizumab in reducing the risk of mortality induced by severe asthma should be considered.
A recent study demonstrated that omalizumab add-on in patients with severe allergic asthma results in a cost-per-quality-adjusted life year ratio that compares favorably with other uses of scarce healthcare resources that are recommended by national reimbursement bodies and could be considered cost-effective. In the current climate of scarce healthcare resources, it is important to demonstrate both economic value as well as therapeutic value of a treatment (Brown 2007). Omalizumab offers both therapeutic and economic value and represents a major advance for the treatment of patients with inadequately controlled severe persistent allergic asthma.
Go to:
References
Adelroth E, Rak S, Haahtela T, et al. Recombinant humanized mAb E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2000;106:253–9. [PubMed] [Google Scholar]
Antonicelli L, Bucca C, Neri M, et al. Asthma severity and medical resource utilization. Eur Respir J. 2004;23:723–729. [PubMed] [Google Scholar]
Ayres JG, Higgins B, Chilvers ER, et al. Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergis asthma. Allergy. 2004;59:7018. [PubMed] [Google Scholar]
Bateman ED, Boushey HA, Bousquet J, et al. Can guideline- defined asthma control be achieved? The Gaining Optiman Asthma ControL study. Am J Resp Crit Care Med. 2004;170:836–44. [PubMed] [Google Scholar]
Boulet L-P, Chapman KR, Cote J, et al. Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response. Am J Respir Crit Care Med. 1997;155:1835–40. [PubMed] [Google Scholar]
Bousquet J, Cabrera P, Berkman N, et al. Effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma. Allergy. 2005;60:302–8. [PubMed] [Google Scholar]
Brown R, Turk F, Dale P, et al. Cost-effectivenes of omalizumab in patients with severe persistent allergic asthma. Allergy. 2007;62:149–53. [PubMed] [Google Scholar]
Buhl R, Hanf G, Soler M, et al. The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma. Eur Respir J. 2002;20:1088–94. [PubMed] [Google Scholar]
Buhl R, Soler M, Matz J, et al. Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma. Eur Respir J. 2002;20:73–8. [PubMed] [Google Scholar]
Busse WW, Banks-Schiegel S, Wenzel S. Pathophysiology of severe asthma. J Allergy Clin Immunol. 2000;106:1033–42. [PubMed] [Google Scholar]
Busse WW, Coffman RL, Gelfand EW, et al. Mechanisms of persistent airway inflammation in asthma. A role for T cells and T-cell products. Am J Respir Crit Care Med. 1995;152:388–93. [PubMed] [Google Scholar]
Casale T. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol. 2006;117:134–40. [PubMed] [Google Scholar]
Casale T, Condemi J, Miller SD, et al. rhuMAb-E25 in the treatment of seasonal allergic rhinitis (SAR) Ann Allergy Asthma Immunol. 1999;82:75. [Google Scholar]
Chang TW. The pharmacological basis of anti-IgE therapy. Nat Biotechnol. 2000;18:157–63. [PubMed] [Google Scholar]
Chang TW, Shiung YY. Anti-IgE as a mastcell stabilizing therapeutic agent. J Allergy Clin Immunol. 2006;117:1203–12. [PubMed] [Google Scholar]
Cruz AA, Lima F, Sarinho E, et al. Safety on anti-immunoglobulin E theraphy with omalizumab in allergic patients at risk of geohelminth infection. Clin Exp Allergy. 2007;37:197–207. [PMC free article] [PubMed] [Google Scholar]
D'Amato G. Therapy of allergic bronchial asthma with anti-IgE monoclonal antibody. Expert Opin Biol Ther. 2003;3:371–6. [PubMed] [Google Scholar]
D'Amato G. Role of anti-igE monoclonal antibody (omalizumab) in the treatment of allergic respiratory diseases. Eur J Pharmacol. 2006;533:302–7. [PubMed] [Google Scholar]
D'Amato G, Bucchioni E, Oldani V, et al. Treating moderate-to-severe allergic asthma with a recombinant humanized anti-IgE monoclonal antibody (omalizumab) Treat Respir Med. 2006;5:393–8. [PubMed] [Google Scholar]
D'Amato G, Holgate ST. The impact of air pollution on respiratory health. Sheffield UK: European Respiratory Monograph; 2002. n.21. [Google Scholar]
D'Amato G, Liccardi G, Noschese P, et al. Anti-IgE. Monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases. Curr Drug Targets Inflamm Allergy. 2004;3:227–9. [PubMed] [Google Scholar]
Deniz Y, Gupta N. Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody. Clin Reviews Allergy Immunol. 2005;29:31–48. [PubMed] [Google Scholar]
Djukanovic R, Wilson SJ, Kraft M, et al. The effects of anti-IgE (omalizumab) treatment on airways inflammation in allergic asthma. Am J Respir Crit Care Med. 2004;170:583–93. [PubMed] [Google Scholar]
European Respiratory Society and the European Lung Foundation. European Lung white book. Brussels, Belgium: European Repiratory Society and The European Lung Foundation; 2003. [Google Scholar]
Fahy JV. The anti-IgE treatment strategy for asthma. In: Yeadon M, Diamant Z, editors. New and exploratory therapeutic agents for asthma: lung biology in health and disease. Marcel Dekker; 2000. pp. 329–42. [Google Scholar]
Fahy JV, Fleming HE, Wong HH, et al. The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects. Am J Respir Crit Care Med. 1997;155:1828–34. [PubMed] [Google Scholar]
Fregonese L, Pael A, van Schadewijk A, et al. Expression of the high affinity IgE receptor (FceRI) is increased in fatal asthma [abstract] Am J Respir Crit Care Med. 2004;169:A297. [Google Scholar]
Godard P, Chanez L, Siraudin L, et al. Costs of asthma are correlated with severity: a 1-yr prospective study. Eur Respir J. 2002;18:61–7. [PubMed] [Google Scholar]
Guite HF, Dundas R, Burney PGJ. Risk factors for death from asthma, chronic obstructive pulmonary disease, and cardiovascular disease after a hospital admission for asthma. Thorax. 1999;54:302–7. [PMC free article] [PubMed] [Google Scholar]
Hamilton RG, Marcotte GV, Saini SS. Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy. J Immunol Methods. 2005;303:81–91. [PubMed] [Google Scholar]
Holgate S, Bousquet J, Wenzel S, et al. Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality. Curr Med Res Opin. 2001;17:233–40. [PubMed] [Google Scholar]
Holgate S, Casale T, Wenzel S, et al. The anti-inflammatory effects of omalizumab confirm the central role of IgE in allergic inflammation. J Allergy Clin Immunol. 2005;115:459–65. [PubMed] [Google Scholar]
Hollowaj JA, Holgate ST, Semper AE. Expression of the high-affinity IgE receptor on peripheral blood dendritic cells: differential binding of IgE in atopic asthma. J Allergy Clin Immunol. 2001;107:1009–18. [PubMed] [Google Scholar]
Holt PG, Macaubas C, Stumbles PA, et al. The role of allergy in the development of asthma. Nature. 1999;402:B1–17. [PubMed] [Google Scholar]
Humbert M, Beaskey R, Ayres J, et al. Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE. Allergy. 60:309–16. [PubMed] [Google Scholar]
Kopp MV, Brauburger J, Riedinger F, et al. The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002;110:728–35. [PubMed] [Google Scholar]
Kuehr J, Brauburger J, Zielen S, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol. 2002;109:274–80. [PubMed] [Google Scholar]
Loddenkemper R, Gibson GJ, Sibille Y, editors. European lung white book. The first comprehensive survey on respiratory health in Europe. European Respiratory Society (ERS) ERSJ. 2003 [Google Scholar]
Mankad SV, Burks AW. Omalizumab: other indications and unanswered questions. Clin Reviews in Allergy Immunol. 2005;29:17–30. [PubMed] [Google Scholar]
MacGlashan DW, Bochner BS, Adelman DC, et al. Down-regulation of FceRI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol. 1997;158:1438–45. [PubMed] [Google Scholar]
Masoli M, Fabian D, Holt S, et al. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 2004;59:468–78. [PubMed] [Google Scholar]
Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab) Pediatrics. 2001;108:36–45. [PubMed] [Google Scholar]
Moore WC, Bleecker ER, Curran-Everett D, et al. Characterization of the severe asthma phenotype by the National Heart, Lung and Blood Institute's Severe asthma Research Program. J Allergy Clin Immunol. 2007;119:405–13. [PMC free article] [PubMed] [Google Scholar]
National Institutes of Health/National Heart Lung and Blood Institute (NHLBI) Global Initiate for Asthma. Global Strategy for Asthma Management and Prevention NHLBI/WHO Workshop Report March 2006. Bethesda, MD, USA: 2006. [Google Scholar]
Niebauer K, Dewilde S, Fox-Rushby J, et al. Impact of omalizumab on quality-of-life outcomes in patients with moderate-to-severe allergic asthma. Ann Allergy Asthma Immunol. 2006;96:316–26. [PubMed] [Google Scholar]
Novak N, Bieber T. Allergic and nonallergic forms of atopic diseases. J Allergy Clin Immunol. 2003;112:252–62. [PubMed] [Google Scholar]
Partridge MR, van der Molen T, Myrseth SE, et al. Attitudes and action of asthma patients on regular maintenance theraphy: the INSPIRE study. BMC Pulm Med. 2006;6:13. [PMC free article] [PubMed] [Google Scholar]
Plewako H, Arvidsson M, Petruson K, et al. The effect of omalizumab on nasal allergic inflammation. J Allergy Clin Immunol. 2002;110:68–71. [PubMed] [Google Scholar]
Rabe KF, Adachi M, Lai CK, et al. Worldwide severity and control of asthma in children and adults: the global asthma insights and reality surveys. J Allergy Clin Immunol. 2004;114:40–7. [PubMed] [Google Scholar]
Redd SC. Asthma in the Unites States: burden and current theories. Environ Health Perspect. 2002;110(Suppl 4):557–60. [PMC free article] [PubMed] [Google Scholar]
Serra-Batles J, Plaza V, Morejon E, et al. Costs of asthma according to the degree of severity. Eur Respir J. 1998;12:1322–6. [PubMed] [Google Scholar]
Soler M, Matz J, Townley R, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J. 2001;18:254–61. [PubMed] [Google Scholar]
Strunk RC, Bloomberg GR. Omalizumab for asthma. New Engl J Med. 2006;354:2689–95. [PubMed] [Google Scholar]
Togias A, Corren J, Shapiro G, et al. Anti-IgE treatment reduces skin test (ST) reactivity. J Allergy Clin Immunol. 1998;101:S171. [Google Scholar]
Tough SC, Hessel PA, Ruff M, et al. Features that distinguish those who die from asthma from community controls with asthma. J Asthma. 1998;35:657–65. [PubMed] [Google Scholar]
Turk F, Kay S, Higgins V. The economic and human impact of poor control in patients with severe persistent allergic asthma: results from a multinational study. Thorax. 2005;60(Suppl 11):21. [Google Scholar]
Vignola AM, Humbert M, Bousquet J, et al. Efficacy and tolerability of anti-immunoglobulin E therapy with olamizumab in patients with concomitant allergic asthma and persistent allergic rhinitis: SOLAR. Allergy. 2004;59:709–17. [PubMed] [Google Scholar]
Van Ganse E, Laforest L, Pietri G, et al. Persistent asthma: disease control, resource utilisation and direct costs. Eur Respir J. 2002;20:260–7. [PubMed] [Google Scholar]
Walker S, Monteil M, Phelan K, et al. Anti-IgE for chronic asthma in adults and children (Review) The Cochrane Collaboration 2006. Issue 2. John Wiley & Sons, Ltd; [PubMed] [Google Scholar]
Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149–60. [PubMed] [Google Scholar]
Wenzel SE, Westcott JY, Larsen GL. Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma: relationship to the development of late asthmatic responses. J Allergy Clin Immunol. 1991;87:540–8. [PubMed] [Google Scholar]
Articles from Therapeutics and Clinical Risk Management are provided here courtesy of Dove Press
Formats:
Article | PubReader | ePub (beta) | PDF (107K) | Cite
Share
Share on Facebook FacebookShare on Twitter TwitterShare on Google Plus Google+
Save items
View more options
Similar articles in PubMed
A recombinant humanized anti-IgE monoclonal antibody (omalizumab) in the therapy of moderate-to-severe allergic asthma.
[Recent Pat Inflamm Allergy Dru...]
Treating Moderate-to-Severe Allergic Asthma with a Recombinant Humanized Anti-IgE Monoclonal Antibody (Omalizumab).
[Treat Respir Med. 2006]
Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a review.
[Multidiscip Respir Med. 2014]
Treating moderate-to-severe allergic asthma with anti-IgE monoclonal antibody (omalizumab). An update.
[Eur Ann Allergy Clin Immunol. ...]
Anti-IgE monoclonal antibody (omalizumab) in the treatment of atopic asthma and allergic respiratory diseases.
[Curr Drug Targets Inflamm Alle...]
See reviews...
See all...
Cited by other articles in PMC
An Omalizumab Biobetter Antibody With Improved Stability and Efficacy for the Treatment of Allergic Diseases
[Frontiers in Immunology. 2020]
International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis
[International forum of allergy...]
Safety and Tolerability of Omalizumab, A Randomized Clinical Trial of Humanized anti-IgE Monoclonal Antibody in Systemic Lupus Erythematosus (STOP LUPUS).
Cutaneous and Gastrointestinal Symptoms in Two Patients with Systemic Mastocytosis Successfully Treated with Omalizumab
[Case Reports in Medicine. 2015]
Janus Kinase-3 Dependent Inflammatory Responses in Allergic Asthma
[International immunopharmacolo...]
See all...
Links
Compound
MedGen
PubMed
Substance
Recent Activity
ClearTurn Off
A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for seve...
A review of anti-IgE monoclonal antibody (omalizumab) as add on therapy for severe allergic (IgE-mediated) asthma
Therapeutics and Clinical Risk Management. 2007 Aug; 3(4)613
Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate t...
Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells
NIHPA Author Manuscripts. Mar–Apr 2008; 22(2)115
See more...
Expression of the high-affinity IgE receptor on peripheral blood dendritic cells: differential binding of IgE in atopic asthma.
[J Allergy Clin Immunol. 2001]
Can guideline-defined asthma control be achieved? The Gaining Optimal Asthma ControL study.
[Am J Respir Crit Care Med. 2004]
Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study.
[BMC Pulm Med. 2006]
See links ...
Review Asthma in the United States: burden and current theories.
[Environ Health Perspect. 2002]
Review Omalizumab for asthma.
[N Engl J Med. 2006]
Asthma severity and medical resource utilisation.
[Eur Respir J. 2004]
Inhibitory effects of an anti-IgE antibody E25 on allergen-induced early asthmatic response.
[Am J Respir Crit Care Med. 1997]
The effect of an anti-IgE monoclonal antibody on the early- and late-phase responses to allergen inhalation in asthmatic subjects.
[Am J Respir Crit Care Med. 1997]
Review The pharmacological basis of anti-IgE therapy.
[Nat Biotechnol. 2000]
Efficacy of omalizumab, an anti-immunoglobulin E antibody, in patients with allergic asthma at high risk of serious asthma-related morbidity and mortality.
[Curr Med Res Opin. 2001]
See more ...
Review The pharmacological basis of anti-IgE therapy.
[Nat Biotechnol. 2000]
Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody.
[J Immunol. 1997]
Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.
[J Allergy Clin Immunol. 2006]
Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis.
[J Allergy Clin Immunol. 2000]
See more ...
Efficacy and tolerability of anti-immunoglobulin E therapy with omalizumab in patients with poorly controlled (moderate-to-severe) allergic asthma.
[Allergy. 2004]
Review Safety and tolerability of omalizumab (Xolair), a recombinant humanized monoclonal anti-IgE antibody.
[Clin Rev Allergy Immunol. 2005]
Review Impact of omalizumab on quality-of-life outcomes in patients with moderate-to-severe allergic asthma.
[Ann Allergy Asthma Immunol. 2006]
Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis.
[J Allergy Clin Immunol. 2006]
Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis.
[J Allergy Clin Immunol. 2000]
The effect of omalizumab on nasal allergic inflammation.
[J Allergy Clin Immunol. 2002]
See more ...
See links ...
The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma.
[Allergy. 2005]
Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.
[Allergy. 2005]
The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma.
[Allergy. 2005]
Review Anti-IgE for chronic asthma in adults and children.
[Cochrane Database Syst Rev. 2006]
Safety of anti-immunoglobulin E therapy with omalizumab in allergic patients at risk of geohelminth infection.
[Clin Exp Allergy. 2007]
Immunological methods for quantifying free and total serum IgE levels in allergy patients receiving omalizumab (Xolair) therapy.
[J Immunol Methods. 2005]
Cost-effectiveness of omalizumab in patients with severe persistent allergic asthma.
[Allergy. 2007]
Support CenterSupport Center
External link. Please review our privacy policy.
NLMNIHDHHSUSA.gov
National Center for Biotechnology Information, U.S. National Library of Medicine
8600 Rockville Pike, Bethesda MD, 20894 USA
Policies and Guidelines | Contact
Η ομαλιζουμάμπη (omalizumab) είναι εξανθρωποποιημένο μονοκλωνικό αντίσωμα που προκύπτει από ανασυνδυασμένο DNA, το οποίο δεσμεύει εκλεκτικά την ανθρώπινη ανοσοσφαιρίνη Ε (IgE). Η ομαλιζουμάμπη δεσμεύεται με την IgE και εμποδίζει τη σύνδεση της IgE με τον FcsRI (υποδοχέας IgE υψηλής συγγένειας) και κατά συνέπεια μειώνει την ποσότητα ελεύθερης IgE που είναι διαθέσιμη για να δώσει το έναυσμα για τον αλλεργικό καταρράκτη. Η αγωγή των ατοπικών ατόμων με ομαλιζουμάμπη είχε ως αποτέλεσμα μια σημαντική προς τα κάτω ρύθμιση των υποδοχέων FcsRI στα βασεόφιλα.
Ανατομική/θεραπευτική/χημική (ATC) ταξινόμηση
Κωδικός
Τίτλος
Κατηγοριοποίηση
R03DX05
Omalizumab
R Αναπνευστικό σύστημα → R03 Φάρμακα για τις αποφρακτικές παθήσεις των αεροφόρων οδών → R03D Άλλα φάρμακα για τις αποφρακτικές παθήσεις των αεροφόρων οδών, για συστηματική χορήγηση → R03DX Λοιπά φάρμακα για τις αποφρακτικές παθήσεις των αεροφόρων οδών, για συστηματική χορήγηση
Κεφάλαια συνταγολογίου ΕΟΦ
Αριθμός
Τίτλος
Κατηγοριοποίηση
03.01.05.03
Ομαλιζουμάμπη (Omalizumab)
03 Φάρμακα παθήσεων αναπνευστικού συστήματος → 03.01 Βρογχοδιασταλτικά (φάρμακα για την αντιμετώπιση βρογχικού άσθματος και χρόνιων αποφρακτικών πνευμονοπαθειών) → 03.01.05 Προφυλακτικά του άσθματος
Πηγή: Γαληνός Οδηγός Φαρμάκων |
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,