Anti-IgE in allergic asthma and rhinitis: an update

Allergic asthma and rhinitis imposes a huge burden in terms of treatment costs, productivity loss and hospital admissions. IgE plays a significant role in the manifestation of these conditions and the identification of a monoclonal antibody that binds to IgE provides clinicians another therapeutic strategy in the management of these conditions. Blocking the effects of IgE by omalizumab, a recombinant humanized monoclonal antibody that selectively binds to IgE has been shown to be a useful adjunct in the treatment of allergic asthma and rhinitis. Omalizumab is effective as a steroid reducing agent in patients with severe asthma and is successful in decreasing asthma exacerbations. Omalizumab was well tolerated in clinical trials, however, the potential long-term side effects need careful monitoring. The high cost of the molecule could make this a therapeutic option in a small proportion of patients in whom there is a large unmet need.     

Therapy of allergic bronchial asthma with omalizumab - an anti-IgE monoclonal antibody

The immunoglobulin E (IgE) antibody plays a central role in the allergic immune responses, such as those which characterise allergic bronchial asthma. The ability to reduce circulating IgE by using anti-IgE antibodies represents a novel therapeutic approach for IgE-mediated allergic diseases. Omalizumab (rhuMAb-E25/Xolair Genentech, USA/Tanox, Inc., USA/Novartis Pharma AG, Switzerland) is a non-anaphylactogen humanised murine monoclonal antibody which binds to circulating IgE. Therapeutic use of an anti-IgE antibody in the treatment of asthma was first suggested in preliminary studies in which omalizumab demonstrated efficacy in attenuating both the early- and late-phase bronchial responses to inhaled allergens in atopic subjects. Treatment with omalizumab has demonstrated both a significant beneficial effect on a number of measures, and a favourable safety profile. It reduces the frequency of asthma exacerbations and the need for inhaled corticosteroids (ICSs), and improves asthma symptoms, lung function and quality of life. The anti-IgE approach to asthma treatment has a number of further potential advantages, such as the treatment of other concomitant atopic diseases (allergic conjunctivitis and rhinitis, atopic dermatitis and food allergy), regardless of the type of allergic sensitisation (seasonal or perennial). On the basis of several studies, omalizumab is likely to provide a new strategy for treating atopic asthma.     

Therapy of allergic bronchial asthma with omalizumab – an anti-IgE monoclonal antibody

The immunoglobulin E (IgE) antibody plays a central role in the allergic immune responses, such as those which characterise allergic bronchial asthma. The ability to reduce circulating IgE by using anti-IgE antibodies represents a novel therapeutic approach for IgE-mediated allergic diseases. Omalizumab (rhuMAb-E25/Xolair?; Genentech, USA/Tanox, Inc., USA/Novartis Pharma AG, Switzerland) is a non-anaphylactogen humanised murine monoclonal antibody which binds to circulating IgE. Therapeutic use of an anti-IgE antibody in the treatment of asthma was first suggested in preliminary studies in which omalizumab demonstrated efficacy in attenuating both the early- and late-phase bronchial responses to inhaled allergens in atopic subjects. Treatment with omalizumab has demonstrated both a significant beneficial effect on a number of measures, and a favourable safety profile. It reduces the frequency of asthma exacerbations and the need for inhaled corticosteroids (ICSs), and improves asthma symptoms, lung function and quality of life. The anti-IgE approach to asthma treatment has a number of further potential advantages, such as the treatment of other concomitant atopic diseases (allergic conjunctivitis and rhinitis, atopic dermatitis and food allergy), regardless of the type of allergic sensitisation (seasonal or perennial). On the basis of several studies, omalizumab is likely to provide a new strategy for treating atopic asthma.     

Omalizumab, a monoclonal antibody against IgE for the treatment of allergic diseases

Omalizumab, a recombinant, humanised monoclonal antibody against human IgE, will be introduced soon for the treatment of allergic asthma. This antibody binds circulating IgE molecules and inhibits the type I immune response in the lung and other target organs. In the phase II and III studies performed, it demonstrated a significant and important effect in controlling and stabilising asthma by reducing exacerbations and the need for inhaled corticosteroids. The safety and tolerability up to one year of treatment were very good. This new treatment may have a role in patients with difficult-to-control asthma, with recurrent exacerbations, and those with concurrent asthma, nose and eye symptoms.     

Immunoglobulin E: role in asthma and allergic disease: lessons from the clinic

The role of immunoglobulin E (IgE) in allergic asthmatic disease is well established. Allergen-specific IgE binds to its cognate receptors, thus triggering a series of cellular events. These events include presentation of antigen by dendritic cells and the degranulation of mast cells and basophils to release numerous factors that play an integral part in potentiating the disease symptoms. Studies in the mouse indicate that a reduction in IgE levels could lead to significant attenuation of the allergic inflammatory response associated with diseases such as asthma, making IgE a target for the development of new therapeutic agents. Omalizumab (Xolair), a recombinant humanised monoclonal anti-IgE antibody that blocks the interaction of IgE with its receptors, is the first anti-IgE agent to undergo clinical development. Several clinical studies have been performed in adults and children with moderate-to-severe allergic asthma to evaluate the efficacy and safety of this agent, but which have also enabled an insight into the role of IgE in human disease. IgE plays a significant role in a number of allergic conditions including allergic rhinitis and allergies to various substances. Recent data suggests that local IgE production may occur in mucosal tissues and that locally significant concentrations of IgE, not reflected by serum IgE concentrations, indicate that it may play a role in non-atopic as well as atopic disease.     

Immunoglobulin E-mediated airway inflammation is active in most patients with asthma

PURPOSE: To review the role of immunoglobulin E (IgE)-mediated inflammation in the pathogenesis of asthma, limitations of standard therapies, and IgE as a logical target for therapy with omalizumab aimed at attaining asthma symptom control. DATA SOURCES: Review of worldwide scientific literature on the role of IgE-mediated inflammation in patients with asthma, supplemented with a clinical case study. CONCLUSIONS: Clinical trials point to an important role for IgE blocker therapy as an add-on to current therapy to reduce exacerbations and corticosteroid use and to improve quality of life in patients with moderate-to-severe asthma. Omalizumab, a monoclonal antibody that binds IgE, has been shown to be an effective, well-tolerated treatment in these patients. IMPLICATIONS FOR PRACTICE: A significant number of patients with moderate-to-severe asthma do not achieve asthma symptom control, despite adhering to current guidelines-based standards of therapy, including the use of inhaled corticosteroids, beta-agonists, and leukotriene modifiers. None of these therapies directly addresses IgE-mediated inflammation. Therefore, patients with persistent symptoms of moderate-to-severe asthma should be evaluated and considered for therapy with the IgE blocker omalizumab.     

Omalizumab: overview of pharmacology and efficacy in asthma

Background: Omalizumab is a monoclonal, humanized antibody specific for the region of IgE that binds to the high affinity IgE receptor on basophils and mast cells. Subcutaneous administration of omalizumab reduces the serum IgE concentration within hours and reduces the number of high affinity IgE receptors expressed on basophils and mast cells over 8 – 12. weeks Methods: A literature search of PubMed was performed using terms omalizumab or monoclonal and asthma. Results/conclusion: Asthma exacerbations are reduced by 19 – 75% with omalizumab therapy added to inhaled corticosteroid therapy, with or without long acting beta agonists and leukotriene modifiers. Approximately 60% of treated subjects show a response and 12 – 16 weeks are generally needed to evaluate response. Omalizumab is cost-effective if high-risk responders are treated. Side effects include 0.2% frequency of systemic reactions to the injections and 2% of subjects with local injection reactions, which do not usually require treatment.     

Omalizumab for pediatric asthma

Importance to the field: Omalizumab is of proven efficacy in the treatment of severe allergic bronchial asthma and works through inhibiting the activity of IgE and the allergic immune mechanism IgE mediates. It has been demonstrated to be efficacious in children with asthma but is not approved by the FDA for use in children below 12 years of age.

Areas covered in this review: Omalizumab is a 95% humanized monoclonal antibody that binds to circulating IgE at the same site on the Fc domain as the high-affinity IgE receptor, Fc?RI. This blocks the interaction between IgE and mast cells and basophils, thereby preventing the release of inflammatory mediators that cause allergic signs and symptoms.

What the reader will gain: From the review of the literatures and statements from the FDA, Genentec and Novartis, the reader will gain a better appreciation of the value of omalizumab in treatment of severe asthma and the current status of its reported side effects.

Take home message: Omalizumab is of proven efficacy in adults and children with severe asthma and allows a markedly reduced dependence on oral and inhaled corticosteroids and decreased hospitalizations. A potential mechanism of omalizumab's effect on thrombus formation and cardiovascular effect is postulated.     

Omalizumab: a future innovation for treatment of severe ocular allergy?

Conjunctival and corneal manifestations of atopic keratoconjunctivitis (AKC) are chronic, disabling and may be blinding. In common with other allergic diseases, such as asthma and atopic dermatitis, AKC is characterised by an allergen-induced immune response mediated through expression of IgE. The humanised monoclonal IgE antibody Xolair (omalizumab) complexes with free circulating IgE, thereby preventing binding of IgE to FcepsilonRI receptors on immune cells. Omalizumab effectively alleviates the signs and symptoms of asthma. Given the pivotal role of IgE in the allergic cascade, it is hypothesised that omalizumab has potential as an entirely new therapeutic approach to AKC.     

Omalizumab: a future innovation for treatment of severe ocular allergy?

Conjunctival and corneal manifestations of atopic keratoconjunctivitis (AKC) are chronic, disabling and may be blinding. In common with other allergic diseases, such as asthma and atopic dermatitis, AKC is characterised by an allergen-induced immune response mediated through expression of IgE. The humanised monoclonal IgE antibody Xolair^® (omalizumab) complexes with free circulating IgE, thereby preventing binding of IgE to FcεRI receptors on immune cells. Omalizumab effectively alleviates the signs and symptoms of asthma. Given the pivotal role of IgE in the allergic cascade, it is hypothesised that omalizumab has potential as an entirely new therapeutic approach to AKC.     

Omalizumab for treatment of allergic rhinitis

Introduction: Immunoglobulin E (IgE) is a key pathogenic factor of allergic rhinitis, a prevalent disease adversely affecting quality of life and productivity.

Areas covered: Binding of inhaled allergens to IgE on the surface of basophils and mast cells, with subsequent cross-linkage of IgE and aggregation of high-affinity receptors for IgE (Fc?RI), triggers the release of inflammatory mediators, followed by the onset of allergic rhinitis symptoms. Current therapeutic strategies include corticosteroids, mast cell stabilizers, leukotriene receptor antagonists, anticholinergics, antihistamines and allergen immunotherapy. Removal of circulating free IgE by the recombinant humanized monoclonal anti-IgE antibody, omalizumab (Xolair), represents a novel therapeutic approach. Omalizumab selectively binds to the C?3 domain of IgE at the site of Fc?R1 binding, thus blocking binding of IgE to effector cells. We review omalizumab's clinical efficacy, administration, use with immunotherapy and safety in allergic rhinitis.

Expert opinion: Omalizumab may provide a new treatment strategy for allergic rhinitis. The high cost of omalizumab precludes its chronic use for allergic rhinitis and it is not FDA approved for this indication; however, its periodic use may be justified in treatment resistant patients, especially those with seasonal disease.     

Technology evaluation: omalizumab,Genentech/Novartis/Tanox

Genentech, Novartis and Tanox have co-developed Genentech's anti-IgE humanized monoclonal antibody omalizumab for the treatment of allergic rhinitis and asthma. The antibody is currently undergoing phase II clinical trials for allergic rhinitis in Canada and phase III clinical trials for both indications in Japan. Omalizumab is at the pre-registration stage for both indications in the US, New Zealand, Switzerland and Western Europe, and is currently registered for both indications in Australia.     

Treatment of allergic diseases with monoclonal anti-IgE antibody]

IgE-mediated mast cell and basophil activation initiates immediate and late-phase allergic responses, and plays a pivotal role in the pathogenesis of allergic diseases such as bronchial asthma and allergic rhinitis. Thus, the blocking of the binding of IgE to the high affinity receptors for IgE (Fc epsilon RI) on mast cells and basophils may prevent dual responses, and improve allergic symptoms. A recombinant humanized monoclonal antibody (rhuMAb-E25) forms complexes with free IgE, blocks its binding to mast cells and basophils, and inhibits allergen-induced mediator release from both cells and attenuates immediate and late-phase reactions to inhaled allergens. In clinical trials, the therapy with rhuMAb-E25 was effective in patients with atopic asthma and allergic rhinitis and well tolerated. This antibody seems to be promising as a treatment for atopic asthma and allergic rhinitis.     

Omalizumab,a novel anti-IgE therapy in allergic disorders

The incidence of allergic diseases is increasing to epidemic proportions both in the developed and developing world with increasing medical costs and lost productivity. The discovery of immunoglobulin (Ig) E heralded a new era in pathophysiological understanding of allergic disorders. Twenty-five years later, a humanised, non-anaphylactogenic antibody was developed against IgE that could provide a therapeutic alternative to the existing medications. RhuMAb-E25 (omalizumab, Xolair^®, Genetech, Inc.) is a novel anti-IgE antibody that is directed against the receptor-binding domain of IgE. This binding is specific towards free IgE thereby preventing it from attaching to the mast cell and its subsequent activation. Initial studies demonstrated attenuation of the early and late asthmatic responses when anti-IgE was administered to asthmatic subjects. Later this novel molecule was found to improve symptom scores, rescue medication use, quality of life scores and peak expiratory flows in patients with allergic asthma. Most importantly, omalizumab treatment reduced the corticosteroid use in asthmatic individuals. In patients with seasonal allergic rhinitis, there was a significant reduction in the nasal and ocular symptoms as well as the use of rescue medications. Omalizumab also demonstrated a high level of safety in adults, adolescents and children with a side effect profile no different from the placebo. Its development is an exciting milestone in the treatment of allergic diseases.     

单克隆抗体靶向治疗儿童严重支气管哮喘的研究现状

单克隆抗体是儿童严重哮喘的一种新型治疗方法,主要通过选择性作用于哮喘炎症级联反应中的特定细胞因子或途径,阻断炎症反应,从而降低哮喘急性发作次数、减少药物用量,并且改善肺功能。其主要不良反应包括注射部位反应及上呼吸道感染等。目前可用于儿童的单克隆抗体包括Omalizumab、Mepolizumab、Benralizuma...     

Ligelizumab for the treatment of chronic spontaneous urticaria

ABSTRACT

Introduction

Due to daily hives with itch, sleeplessness, and unforeseen development of angioedema, chronic spontaneous urticaria significantly impairs quality of life, often for years. Its management is challenging. In most cases, H1-antihistamines are not effective. Although the disease is not characterized by specific IgE antibodies against allergens, the last decade demonstrated that neutralizing IgE by using the monoclonal anti-IgE antibody Omalizumab is safe and effective. Nevertheless, symptoms are not controlled by Omalizumab in approximately one-fourth of patients.     

Omalizumab: a novel therapy for allergic asthma

OBJECTIVE: To review the pharmacology, efficacy, and safety of omalizumab, focusing on the treatment of allergic asthma. DATA SOURCES: A MEDLINE search (1966-November 2003) was conducted using the key words omalizumab, Xolair, and Rhu-MAB25, with studies limited to those in humans and published in English. References of identified articles were reviewed for additional citations. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the pharmacology, efficacy, and safety of omalizumab for treatment of allergic asthma in patients aged >or=12 years were selected. Clinical trials examining utility in pediatric patients were also reviewed. DATA SYNTHESIS: Omalizumab's ability to form complexes with unbound immunoglobulin E (IgE) translates into decreased unbound serum IgE levels and high-affinity IgE receptors on basophils, as well as attenuation of early and late allergic response in patients with allergic asthma. Results of clinical trials demonstrated that omalizumab administered subcutaneously is a safe and effective treatment for moderate to severe allergic asthma. Generally, omalizumab has a mild adverse effect profile. Omalizumab may be particularly useful for treatment of moderate to severe allergic asthma in patients who are poorly controlled on conventional therapy, experience adverse effects secondary to high-dose or prolonged corticosteroid treatment, or who have frequent exacerbations because of poor medication adherence. The high cost associated with omalizumab treatment may be prohibitive for some patients, thereby limiting its utility. CONCLUSIONS: Omalizumab is a safe and effective therapy for treatment of moderate to severe allergic asthma in difficult-to-treat, high-risk patients.     

Precipitating factors in respiratory allergic disease in Indonesian children.

Skin test results and IgE antibody levels measured by RAST indicate that hypersensitivity to house dust mite (D. pteronyssinus) is a major feature of asthma and allergic rhinitis in Indonesian children. Total serum IgE levels were higher in the allergic than in control children. 60% (twenty-one out of thirty-five) of the asthmatic children and 56% (five out of nine) of the children with allergic rhinitis had IgE antibodies to the helminth Ascaris lumbricoides compared with none out of four control children. A tendency was found for high IgE antibody levels to D. pteronyssinus to occur in association with low IgE antibody levels to A. lumbricoides and vice versa.     

Omalizumab: where does it fit into current asthma management?

Omalizumab (Xolair), a monoclonal antibody, is a new agent that blocks the allergic cascade at its primary step. This drug offers substantial promise for patients with moderate-to-severe, persistent allergic asthma that is not well controlled. But due to the cost of the drug, limitations on dosage, and available clinical trial data, it is not a first-line therapy. This review discusses how this drug works, which patients will be candidates for it, and the practical aspects of using it.     

Monoclonal antibodies for the treatment of asthma

Asthma is a chronic inflammatory disease of the airways which can have a detrimental effect on quality of life and in extreme cases cause death. Although the majority of patients can control their asthma symptoms with a combination of steroids and beta agonists there is still a group of patients whose asthma remains symptomatic despite the best available treatment. These severe asthmatic patients represent the unmet medical need in asthma and are the focus of those developing novel monoclonal antibody based drugs. The complex networks of cytokines and cells involved in the pathology of asthma provide plenty of scope for intervention with monoclonal antibody based drugs which are able to block cytokine or chemokine receptor interactions, deplete cells expressing a specific receptor or block cell/cell interactions. At present anti-IgE (Xolair©) is the only monoclonal antibody based drug approved for the treatment of asthma. However, a number of other antibody based drugs have been clinically tested in asthma including anti-IL-5, anti-IL-4, anti-IL-13, anti-TNFα, anti-CCR3, anti-CCR4 and anti-OX40L. This review will examine the development of these monoclonal antibody based therapies. Since many of these therapies have targeted key pathways in asthma pathology these studies provide information on patient stratification and asthma pathology.