Response to omalizumab using patient enrichment criteria from trials of novel biologics in asthma.

BACKGROUND: Recent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy. METHODS: Data from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils <300/µL [low] vs ≥300/µL [high]) and baseline markers of asthma severity (emergency asthma treatment in prior year, asthma hospitalization in prior year, forced expiratory volume in 1 second [FEV1 ; FEV1 <65% vs ≥65% predicted], inhaled beclomethasone dipropionate dose [<600 vs ≥600 µg/day], and long-acting beta-agonist [LABA] use [yes/no]). RESULTS: Adults/adolescents (N = 1071) were randomized to receive either omalizumab (n = 542) or placebo (n = 529). In the 16-week ICS dose-stable phase, rates of exacerbations requiring ≥3 days of systemic corticosteroid treatment were 0.066 and 0.147 with omalizumab and placebo, respectively, representing a relative rate reduction in omalizumab-treated patients of 55% (95% CI, 32%-70%; P = .002). For patients with eosinophils ≥300/µL or with more severe asthma, this rate reduction was significantly more pronounced. CONCLUSION: In patients with allergic asthma, baseline blood eosinophil levels and/or clinical markers of asthma severity predict response to omalizumab.

CYT003, a TLR9 agonist, in persistent allergic asthma - a randomized placebo-controlled Phase 2b study.

BACKGROUND: New treatment options are required for patients with asthma not sufficiently controlled with inhaled therapies. In a Phase 2a trial, CYT003, a Toll-like receptor-9 agonist immunomodulator, improved asthma control during inhaled glucocorticosteroid reduction in patients with allergic asthma. This double-blind Phase 2b study assessed the efficacy and safety of CYT003 in patients with persistent moderate-to-severe allergic asthma not sufficiently controlled on standard inhaled glucocorticosteroid therapy with/without long-acting beta-agonists (LABAs). METHODS: Overall, 365 patients received seven doses of subcutaneous CYT003 (0.3, 1, or 2 mg) or placebo as add-on therapy to conventional controller medication. Change from baseline in Asthma Control Questionnaire (ACQ) score was the primary outcome; secondary outcomes included change in forced expiratory volume, Mini Asthma Quality of Life Questionnaire, and safety. RESULTS: All groups, including placebo, showed a clinically important improvement in ACQ score; however, there was no significant difference between the CYT003 and placebo groups at week 12 (least-squares mean difference 0.3 mg: -0.027 [95% confidence interval -0.259 to 0.204]; 1 mg: 0.097 [-0.131 to 0.325]; 2 mg: 0.081 [-0.148 to 0.315]). No significant differences were seen in secondary outcomes. CYT003 was well tolerated; the most common treatment-emergent adverse events were injection site reactions. Due to lack of efficacy, the study was prematurely terminated at the end of the treatment phase with no further follow-up. CONCLUSIONS: Toll-like receptor-9 agonism with CYT003 showed no additional benefit in patients with insufficiently controlled moderate-to-severe allergic asthma receiving standard inhaled glucocorticosteroid therapy with or without LABAs.

The Asthma Control Questionnaire as a clinical trial endpoint: past experience and recommendations for future use.

The goal of asthma treatment is to control the disease according to guidelines issued by bodies such as the Global Initiative for Asthma. Effective control is dependent upon evaluation of symptoms, initiation of appropriate treatment and minimization of the progressive adverse effects of the disease and its therapies. Although individual outcome measures have been shown to correlate with asthma control, composite endpoints are preferred to enable more accurate and robust monitoring of the health of the individual patient. A number of validated instruments are utilized to capture these component endpoints; however, there is no consensus on the optimal instrument for use in clinical trials. The Asthma Control Questionnaire (ACQ) has been shown to be a valid, reliable instrument that allows accurate and reproducible assessment of asthma control that compares favourably with other commonly used instruments. This analysis provides a summary of the use of ACQ in phase II, III and IV asthma trials. Comparisons between the ACQ and other instruments are also presented. Our analysis suggests that the ACQ is a valid and robust measure for use as a primary or secondary endpoint in future clinical trials.

Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

Allergic Rhinitis and its Impact on Asthma (ARIA): achievements in 10 years and future needs.

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.

International consensus on (ICON) pediatric asthma.

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved.

[ARIA (Allergic Rhinitis and its Impact on Asthma) achievements in 10 years and future needs]. / ARIA (allerjik rinit ve astim üzerine etkisi) 10 yildaki kazanimlar ve gelecekteki gereksinimler.

Allergic rhinitis and asthma represent global health problems for all age groups. Asthma and rhinitis frequently co-exist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization (WHO) workshop in 1999 and was published in 2001. ARIA has reclassified allergic rhinitis as mild/moderate-severe and intermittent/persistent. This classification schema closely reflects the impact of allergic rhinitis on patients. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of allergic rhinitis and asthma co-morbidities based on GRADE (Grading of Recommendation, Assessment, Development and Evaluation). ARIA has been disseminated and implemented in over 50 countries of the world. In Turkey, it is important to make a record of ARIA achievements and to identify the still unmet clinical, research and implementation needs in order to strengthen the 2011 EU Priority on allergy and asthma in children.

Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper.

Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.

Practical guide to skin prick tests in allergy to aeroallergens.

This pocket guide is the result of a consensus reached between members of the Global Allergy and Asthma European Network (GA(2) LEN) and Allergic Rhinitis and its Impact on Asthma (ARIA). The aim of the current pocket guide is to offer a comprehensive set of recommendations on the use of skin prick tests in allergic rhinitis-conjunctivitis and asthma in daily practice. This pocket guide is meant to give simple answers to the most frequent questions raised by practitioners in Europe, including 'practicing allergists', general practitioners and any other physicians with special interest in the management of allergic diseases. It is not a long or detailed scientific review of the topic. However, the recommendations in this pocket guide were compiled following an in-depth review of existing guidelines and publications, including the 1993 European Academy of Allergy and Clinical Immunology position paper, the 2001 ARIA document and the ARIA update 2008 (prepared in collaboration with GA(2) LEN). The recommendations cover skin test methodology and interpretation, allergen extracts to be used, as well as indications in a variety of settings including paediatrics and developing countries.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Development and implementation of guidelines in allergic rhinitis ­ an ARIA-GA2LEN paper.

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved.

Safety and tolerability of omalizumab.

BACKGROUND: Omalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma. OBJECTIVE: To review clinical study data to assess the safety profile of omalizumab. METHODS: We analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia. RESULTS: Omalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57,300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab. CONCLUSION: Data indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.

A new perspective on concepts of asthma severity and control.

Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.

Exercise-induced hypersensitivity syndromes in recreational and competitive athletes: a PRACTALL consensus report (what the general practitioner should know about sports and allergy).

Exercise-induced (EI) hypersensitivity disorders are significant problems for both recreational and competitive athletes. These include EI-asthma, EI-bronchoconstriction, EI-rhinitis, EI-anaphylaxis and EI-urticaria. A group of experts from the European Academy of Allergology and Clinical Immunology and the American Academy of Allergy Asthma and Immunology met to discuss the pathogenesis of these disorders and how to diagnose and treat them, and then to develop a consensus report. Key words (exercise with asthma, bronchoconstriction, rhinitis, urticaria or anaphylaxis) were used to search Medline, the Cochrane database and related websites through February 2008 to obtain pertinent information which, along with personal reference databases and institutional experience with these disorders, were used to develop this report. The goal is to provide physicians with guidance in the diagnosis, understanding and management of EI-hypersensitivity disorders to enable their patients to safely return to exercise-related activities.

CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc epsilon RI.

BACKGROUND: Fc epsilon RI expression by monocytes can affect monocyte function via multiple mechanisms, thereby potentially influencing the generation of allergic inflammation. Previous studies on the in vivo regulation of monocyte Fc epsilon RI expression by ambient IgE have yielded conflicting results. OBJECTIVE: We hypothesized that monocyte Fc epsilon RI expression is limited to a specific monocyte subset, and that within that subset Fc epsilon RI surface expression is correlated to serum IgE. METHODS: Study 1: Blood was obtained from non-allergic subjects (n=14) and subjects with allergic asthma (n=18), hypereosinophilic syndrome (n=2), hyper-IgE syndrome (n=6), and helminth infection (n=4). Study 2: Blood was obtained from allergic subjects in a clinical trial of omalizumab before and during study drug treatment. Monocyte surface Fc epsilon RI expression was measured using flow cytometry. RESULTS: Fc epsilon RI expression was significantly greater in the CD2(high) vs. CD2(low) monocyte subsets (31% vs. 1.9% median Fc epsilon RI+, respectively). In asthmatic and non-atopic healthy control subjects, CD2(low) monocytes expressed little or undetectable Fc epsilon RI. In study 1, Fc epsilon RI expression was highly correlated to serum IgE in the CD2(high), but not in the CD2(low) monocyte subpopulation (R values of 0.67 and 0.41, respectively). In study 2, omalizumab, but not placebo, caused a significant and sustained decline in Fc epsilon RI expression within the CD2(high) monocyte subset. CONCLUSIONS: CD2 defines a monocyte subset with high Fc epsilon RI expression, whose magnitude is highly correlated to serum IgE. As such, this new description of CD2(high) monocytes as Fc epsilon RI-bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies.

Suppression of hypothalamic-pituitary-adrenal axis activity with inhaled flunisolide and fluticasone propionate in adult asthma patients.

BACKGROUND: Suppression of the hypothalamic-pituitary-adrenal (HPA) axis, a potential systemic effect of inhaled corticosteroid therapy, can be quantified by monitoring serum, urinary, and salivary cortisol levels. OBJECTIVES: 1) Compare the effects on HPA axis of the inhaled corticosteroids flunisolide and fluticasone propionate versus placebo and oral prednisone. 2) Estimate dose-potency ratio for HPA-axis suppression. METHODS: Multicenter, randomized, placebo-controlled, open-label, 21-day trial. Active regimens were flunisolide 500 and 1,000 microg, twice daily; fluticasone propionate 110, 220, 330, and 440 microg, twice daily; and prednisone, 7.5 mg daily. Enrolled patients were nonsmokers, 18 to 50 years of age, with persistent mild-to-moderate asthma and had not used oral, nasal, or inhaled corticosteroids for 6 months before study. Main outcome measures were area under serum cortisol concentration curve for 22 hours (AUC(0-22h)); 24-hour urinary cortisol level; and 8 AM salivary cortisol level. RESULTS: One hundred fifty-three patients were randomly assigned to active treatment or placebo; 125 patients completed the study and were at least 80% compliant with their regimens. Both fluticasone propionate and flunisolide caused dose-dependent suppression of HPA axis, which was statistically greater for fluticasone propionate (P = 0.0003). Dose-potency ratio showed 4.4 times more serum-cortisol suppression/microgram increase in dose with fluticasone propionate than with flunisolide. Diurnal pattern of serum cortisol suppression was persistent with fluticasone propionate and "remitting" with flunisolide. Salivary and urinary cortisol data were qualitatively similar to serum cortisol results. CONCLUSIONS: Fluticasone caused significantly more suppression of HPA axis than flunisolide. Flunisolide may provide a safe option for patients with asthma requiring long-term inhaled corticosteroid therapy.

Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial.

CONTEXT: Seasonal allergic rhinitis is a common IgE-mediated disorder that produces troublesome symptoms. A recombinant humanized monoclonal anti-IgE antibody (omalizumab) forms complexes with free IgE, blocking its interaction with mast cells and basophils and lowering free IgE levels in the circulation. OBJECTIVE: To assess the efficacy and safety of omalizumab for prophylaxis of symptoms in patients with seasonal allergic rhinitis. DESIGN: Randomized, double-blind, dose-ranging, placebo-controlled trial conducted from July 25 through November 21, 1997. SETTING: Twenty-five outpatient centers throughout the United States. PATIENTS: Five hundred thirty-six patients aged 12 to 75 years with at least a 2-year history of moderate to severe ragweed-induced seasonal allergic rhinitis and a baseline IgE level between 30 and 700 IU/mL. INTERVENTIONS: Patients were randomly assigned to receive omalizumab, 50 mg (n = 137), 150 mg (n = 134), or 300 mg (n = 129), or placebo (n = 136) subcutaneously just prior to ragweed season and repeated during the pollen season every 3 weeks in patients with baseline IgE levels of 151 to 700 IU/mL (4 total treatments) and every 4 weeks in patients with baseline IgE levels of 30 to 150 IU/mL (3 total treatments). MAIN OUTCOME MEASURES: Self-assessed daily nasal symptom severity scores (range, 0-3), rescue antihistamine use, and rhinitis-specific quality of life during the 12 weeks from the start of treatment. RESULTS: Nasal symptom severity scores were significantly lower in patients who received 300 mg of omalizumab than in those who received placebo (least squares means, 0.75 vs 0.98, respectively; P =.002). A significant association was observed between IgE reduction and nasal symptoms and rescue antihistamine use. Rhinitis-specific quality of life scores were consistently better in patients who received 300 mg of omalizumab than in those who received lower dosages or placebo and did not decline during peak season. The frequency of adverse events was not significantly different among the omalizumab and placebo groups. CONCLUSION: Omalizumab decreased serum free IgE levels and provided clinical benefit in a dose-dependent fashion in patients with seasonal allergic rhinitis.

Anti-immunoglobulin E (omalizumab) therapy in seasonal allergic rhinitis.

Anti-immunoglobulin E (anti-IgE) (omalizumab), a humanized monoclonal anti-IgE antibody that binds to circulating IgE, has been studied in several large double-blind, randomized, placebo-controlled clinical trials to determine its pharmacokinetic characteristics, efficacy, and safety in ragweed- or birch pollen-induced seasonal allergic rhinitis (SAR). The consequences of readministering omalizulab after a lapse of time have also been studied. These studies have confirmed that serum-free IgE declines in a dose-related manner with such treatment and that omalizumab-induced declines in IgE correlate with symptom improvement. Whether omalizumab is administered intravenously or subcutaneously, its pharmacokinetics do not differ. A Phase II dose-ranging study demonstrated that the optimum efficacious dose of omalizumab for the treatment of seasonal allergic rhinitis is 300 mg administered subcutaneously. The dosing frequency, in terms of whether the antibody is administered every 3 or 4 wk, is based on the patient's baseline IgE level. With adequate dosing, nasal and ocular symptoms are significantly reduced, and quality of life is significantly improved. Omalizumab is safe and well tolerated and can be safely readministered in subsequent pollen seasons.

Experience with monoclonal antibodies in allergic mediated disease: seasonal allergic rhinitis.

Current therapies for the treatment of seasonal allergic rhinitis include allergen avoidance; pharmacologic interventions such as sympathomimetics, topical and systemic cortico-steroids, and chromones; and immunotherapy. In an attempt to create a novel therapy, therapeutic agents have been designed to inhibit IgE responses that are intimately involved in the induction of the allergic response. Omalizumab, a humanized monoclonal antibody against IgE, represents a novel therapeutic intervention for seasonal allergic rhinitis. Complex formation of omalizumab with serum-free IgE reduces the amount of IgE available for binding to effector cells and thus has the potential to reduce IgE-mediated allergic symptoms. Clinical trial results confirmed that omalizumab reduces free IgE to a level that is associated with suppressed allergic symptoms, reduces concomitant rescue medication use, and improves rhinitis-specific quality of life. Patients treated with omalizumab during one pollen season can be re-treated during the subsequent season with minimal risk of adverse events. Omalizumab is non-allergen-specific and does not induce acute anaphylaxis because of the lack of IgE crosslinking with basophil- or mast-cell-bound IgE. Furthermore, subcutaneous or intravenous administration of omalizumab does not invoke the generation of anti-omalizumab antibodies. Thus, omalizumab represents a novel agent that should assist in the treatment of allergic rhinitis.