Churg-Strauss Vasculitis in a Patient Treated with Omalizumab

Omalizumab is a new anti-IgE treatment for severe-persistent allergic asthma. In this case presentation, we report the clinical features of a patient with Churg-Strauss syndrome (CSS) diagnosed after five months of omalizumab treatment. Administration of anti-IgE quickly improved asthma symptoms and enabled the gradual reduction and suspension of systemic steroids. After the suspension of steroids, vasculitis became evident and CSS was diagnosed. Here, we report the clinical course of this patient to evaluate the efficacy of omalizumab in CSS.     

Clinical Benefits of 7 Years of Treatment with Omalizumab in Severe Uncontrolled Asthmatics

Rationale. Severe asthma is characterized by inadequate symptom control and by high rate of inflammation despite high doses of steroids. Omalizumab, a recombinant humanized monoclonal anti-IgE, provides a new therapeutic strategy in severe allergic asthma. Aims. This study was aimed to assess whether long-term treatment with omalizumab improved clinical control in severe asthmatics. Methods. We investigated omalizumab effects on asthma outcomes evaluating seven severe allergic asthmatic patients who were treated for 7 years with add-on omalizumab. Number of exacerbations, use of antibiotics, additional asthma medications (systemic steroids, nebulized steroids and bronchodilators), and spirometry were analyzed before and after omalizumab treatment. Results. Omalizumab was well tolerated by all the studied patients. It improved FEV1 and FEV1/FVC ratio and reduced symptom score, asthma exacerbations, use of antibiotics, and use of nebulized steroids, bronchodilators, and oral corticosteroids. These effects were evident after 4 years of treatment and more pronounced after 7 years of treatment. Conclusions. This study underlines the utility of a long-term treatment with omalizumab to improve asthma clinical outcomes in severe asthmatics.     

Treatment of asthma with antileukotrienes and Churg-Strauss syndrome

Since antileukotriene treatment for asthma was introduced, there has been debate about whether such therapy can lead to Churg-Strauss Syndrome (CSS) or whether CSS is simply inhibited by the use of steroids, as various authors have suggested. We report a case in which we suspected CSS in a patient with bronchopulmonary, cutaneous and analytical signs and whom we treated with oral steroids. After clinical improvement, one year later, steroids were replaced by antileukotrienes, after which the same clinical picture developed. The vasculitis characteristic of CSS was confirmed pathologically.     

Beneficial effects of treatment with anti-IgE antibodies (Omalizumab) in a patient with severe asthma and negative skin-prick test results

It is now well recognized that treatment with anti-IgE antibodies like omalizumab is a valuable option in patients with allergic asthma who remain symptomatic despite optimal treatment. To our knowledge, treatment with omalizumab in patients with nonallergic asthma has not been reported. We present and discuss a patient with severe asthma and elevated total IgE who had a negative radioallergosorbent (RAST) test result and a negative skin-prick test result; the patient showed a dramatic improvement with this treatment strategy.     

Effectiveness of Omalizumab in a Patient with Severe Asthma, Low Serum IgE Level, and Lack of Sensitized Allergens Induced by Oral Steroid Therapy: The Usefulness of Impulse Oscillation for Assessment of Omalizumab Therapy

Background. Omalizumab is a humanized monoclonal anti-IgE antibody that was recently approved for the treatment of severe allergic asthma. However, omalizumab is not licensed for allergic asthma in patients with a low serum IgE level (<30 IU/mL) or negative results for specific allergen tests. Case history. We present a patient with severe asthma and low serum IgE levels who had negative results for specific allergens induced by oral steroid therapy. Omalizumab administration improved asthma exacerbated forced expiratory volume in 1 s (FEV(1)) and respiratory resistance measurements based on the impulse oscillation technique (Mostgraph-01). The response to omalizumab therapy was evidenced by a decrease in airway resistance at 1 month. Conclusions. The findings of this case report indicate that omalizumab treatment had beneficial effects in a patient with severe asthma and low total serum IgE levels with negative results for specific IgE, which may have been induced by long-term corticosteroid administration.     

Biologic treatment eligibility for real-world patients with severe asthma: The IDEAL study

Objectives: Severe asthma comprises several distinct phenotypes. Consequently, patients with severe asthma can be eligible for more than one biologic treatment targeting Th2 inflammation, such as anti-interleukin (IL)-5 and anti-immunoglobulin (Ig) E. The objective of this study was to describe treatment eligibility and overlap in treatment eligibility for mepolizumab (anti-IL-5), omalizumab (anti-IgE) and reslizumab (anti-IL-5) in patients with severe asthma, who were recruited from clinical practice. Methods: This cross-sectional, single-visit, observational study in six countries enrolled patients with severe asthma (defined by American Thoracic Society/European Respiratory Society guidelines). Assessable patients were analysed as a total cohort and a sub-cohort, who were not currently receiving omalizumab. Treatment eligibility was defined according to the local prescribing information or protocol-defined inclusion/exclusion criteria. Patients currently receiving omalizumab were automatically categorised as omalizumab-eligible. Results: The total cohort comprised 670 patients who met the analysis criteria, of whom 20% were eligible for mepolizumab, 31–41% were eligible for omalizumab (depending on eligibility criteria used), and 5% were eligible for reslizumab. In patients not currently receiving omalizumab (n = 502), proportions eligible for each biologic were similar (mepolizumab: 20%, reslizumab 6%) or lower (omalizumab 7–21%) than those for the total cohort. Overlap in treatment eligibility varied; in mepolizumab-eligible patients not currently receiving omalizumab (n = 101), 27–37% were omalizumab-eligible and 18% were reslizumab-eligible. Conclusions: Treatment eligibility for mepolizumab and omalizumab was higher than that for reslizumab. Although there was some overlap in treatment eligibility, the patient groups eligible for treatment with anti-IL-5 or anti-IgE therapies were often distinct, emphasising the different phenotypes and endotypes in severe asthma.     

Omalizumab treatment of systemic mast cell activation disease: experiences from four cases

We report on the outcome of 4 patients with therapy-resistant systemic mast cell activation disease (MCAD) treated with the anti-IgE monoclonal antibody omalizumab in compassionate use. Two patients achieved an impressive persistent clinical response to treatment with omalizumab. In the third patient symptoms gradually improved. In the fourth patient omalizumab treatment had to be discontinued due to intolerable mast cell mediator-induced symptoms. In conclusion, omalizumab can lessen the intensity of the symptoms of systemic MCAD. Hence, omalizumab should be considered as a therapeutic option in cases of systemic MCAD that are resistant to evidence-based therapy.     

Anti-IgE in severe persistent allergic asthma

Abstract:   Omalizumab is an mAb targeted against IgE. It reduces asthma exacerbations and symptoms and has low anaphylactic potential. In the placebo-controlled double-blind study, INNOVATE, omalizumab was used in the patient population with the greatest unmet clinical need, who being those meeting the Global Initiative for Asthma 2002 step 4 criteria for severe persistent asthma. When added to existing therapy, patients treated with omalizumab had a 26.2% lower rate of clinically significant asthma exacerbations, after an adjustment to take into account an observed pre-study imbalance in the exacerbation rate ( P  = 0.042). The Global Initiative for Asthma has recognized the role of anti-IgE therapy in treating patients with severe persistent asthma. Initiation of anti-IgE therapy is now recommended for these patients at step 4. Severe asthma has a major impact on health-care resource utilization. To date, treatment options have been limited in this target population. Omalizumab reduces symptoms, exacerbations and emergency visits in patients who are not adequately controlled on inhaled corticosteroids and long-acting beta agonists. It is a valuable therapeutic option, addressing an unmet need in the area of severe asthma.     

Omalizumab treatment in asthma-COPD overlap syndrome

Introduction: Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS) is a poorly understood disease with an increasing morbidity and mortality. Currently, the most effective treatment for ACOS is unknown and omalizumab for ACOS has not yet been reported. Methods: We report our experience with anti-IgE, omalizumab treatment on 3 patients with ACOS as a retrospective case study. Results: After 1 year of omalizumab treatment, patients experienced significantly lower rates of asthma exacerbation and hospitalization and better asthma control test results. Conclusion: Our study shows that omalizumab may be an effective and safe therapy for patients with ACOS. However larger randomized trials are needed.     

Case study: A Combination of Mepolizumab and Omaluzimab injections for severe asthma

A Combination of Mepolizumab and Omaluzimab injections for severe asthma. Introduction. Patients with severe persistent asthma account for a large proportion of asthma morbidity and health care expenditures. In this case report we describe the use of a combination of omalizumab and mepolizumab in severe asthma with elevated IgE levels and eosinophilic phenotype. Case Study: We are treating a 55 year old woman with severe persistent eosinophilic asthma and elevated IgE levels. Her regimen included salmeterol/fluticasone propionate inhaler 500/50 one puff twice a day, budesonide nebulizer twice a day, tiotropium respimat inhaler two puffs daily, montelukast 10 mg daily, Albuterol as needed, Azithromycin 250 mg three times a week, and also omalizumab injections. She was having recurrent asthma exacerbations requiring the use of oral corticosteroids. Due to frequent exacerbations, we referred her for Bronchial Thermoplasty. This procedure was denied by insurance and therefore the patient was started on 20 mg PO prednisone daily. Mepolizumab was added approximately 4 months after starting chronic PO prednisone. We were able to taper down the steroids and she is currently on 4 mg daily. Results: Since we added the mepolizumab injections along with the omalizumab injections, we have been able to decrease the prednisone steadily and currently the patient is on 4 mg daily. The plan is to taper off the corticosteroids slowly as the clinical status allows. Conclusion: Combination of omalizumab and mepolizumab could become the gold standard for severe asthma patients that have elevated IgE levels and an eosinophilic phenotype. Case Report: A Combination of Mepolizumab and Omaluzimab injections for severe asthma.     

Omalizumab: Anti-IgE Therapy in Allergy

Omalizumab is a humanized, monoclonal anti-IgE antibody that binds specifically to circulating IgE molecules, thus interrupting the allergic cascade. Omalizumab has been shown to be highly effective in treating children and adults with moderate to severe allergic asthma. Beyond this indication, the mode of action itself suggests that omalizumab is not only an antiasthmatic drug but also a promising therapeutic option for various allergic conditions, including allergic rhinitis, food allergy, urticaria, allergic bronchopulmonary aspergillosis, insect hypersensitivity, and atopic dermatitis. However, data from double-blind, placebo-controlled clinical trials are only available for allergic rhinitis and moderate to severe bronchial asthma. The aim of this review is to discuss the current clinical data as well as possible further indications of omalizumab treatment.     

Treating moderate-to-severe allergic asthma with anti-IgE monoclonal antibody (omalizumab). An update

Increased asthma severity is not only associated with enhanced recurrent hospitalisation and mortality but also with higher social costs. Most cases of asthma are atopic in nature, with the trigger for acute asthma attacks and chronic worsening of inflammation being allergens inducing an immune response through immunoglobulins of IgE class. Currently antiinflammatory treatments are effective for most of asthma patients, but there are subjects whose disease is incompletely controlled by inhaled or systemic corticosteroids and these patients account for about 50% of the healthcare costs of asthma. Omalizumab is a humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases and with clear efficacy in adolescent and adult patients with moderate-to-severe allergic asthma.. The 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 really new approach to the treatment of atopic asthma. Omalizumab improves quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. This therapy is well tolerated and significantly improves symptoms, disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids. In other words, omalizumab may fulfil an important need in patients with moderate-to-severe asthma.     

Anti-IgE antibodies for the treatment of asthma

PURPOSE OF REVIEW: Allergic asthma is a hypersensitivity reaction initiated by immunologic mechanisms mediated by IgE antibodies. IgE plays a central role in the initiation and propagation of the inflammatory cascade and thus the allergic response. Targeting factors involved in the allergic response, such as IgE, is a novel strategy for new therapies. Attenuating allergic disease by specifically inhibiting IgE and the development of the monoclonal anti-IgE antibody, omalizumab, were major breakthroughs in asthma management. RECENT FINDINGS: Several studies have shown that omalizumab has significant anti-inflammatory effects and that it may act on multiple components of the inflammatory cascade. Specific binding of IgE by omalizumab reduces both the early allergic response and the late allergic response and symptoms of IgE-mediated allergy. The long-term clinical efficacy of omalizumab has been demonstrated along with improvements in quality of life. As add-on therapy in severe asthma, omalizumab reduces the requirement for inhaled corticosteroids and improves disease control. Clinical studies have shown that the patients who benefit most from omalizumab therapy are those at high risk of exacerbations, those with poorly controlled and/or severe asthma, and those with IgE-mediated comorbidities. SUMMARY: Omalizumab is a significant addition to current asthma treatments and shows great promise as a therapy for allergic asthma and for patients with concomitant allergic rhinitis. This is particularly true for difficult-to-treat patients with moderate to severe allergic asthma who have poorly controlled disease on conventional therapies, experience severe adverse effects secondary to high-dose or prolonged corticosteroid treatment, have frequent exacerbations, and/or are at high risk of hospitalization. Future studies will continue to investigate the anti-inflammatory mechanisms of anti-IgE therapy. Because many of these mechanisms are common to all IgE-mediated allergic diseases, the efficacy of omalizumab in other allergic diseases should be further explored.     

Anti-immunoglobulin E therapy for asthma

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 humanized 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. Treatment with omalizumab was well tolerated and showed clinical benefit in terms of a reduction in the frequency and number of asthma exacerbation episodes and lower usage of corticosteroids and other medications to control disease, along with improved quality of life. Such findings indicate that omalizumab represents a promising new treatment option for allergic asthma.     

Asthme sévère : démarche diagnostique et thérapeutique. À propos d’une observation

Case report

In a 16-year-old teenager hospitalized with a severe asthma attack, the diagnosis of severe asthma associated to allergy and current tobacco smoke and allergen exposure is confirmed. Despite the use of high dose of inhaled antiasthma medication, the disease remains uncontrolled and anti-IgE, omalizumab treatment is started. After few weeks, respiratory symptoms and function dramatically improve.

Conclusion

Severe asthma must be readily diagnosed in order to adapt treatment and avoid fatal outcome or respiratory disability.     

Roles of omalizumab in various allergic diseases

IgE and mast cells play a pivotal role in various allergic diseases, including asthma, allergic rhinitis, and urticaria. Treatment with omalizumab, a monoclonal anti-IgE antibody, has significantly improved control of these allergic diseases and introduced a new era for the management of severe allergic conditions. About 10 years of experience with omalizumab treatment for severe allergic asthma confirmed its effectiveness and safety, reducing symptoms, frequency of reliever use, and severe exacerbations in patients with intractable conditions. Omalizumab is particularly useful in childhood asthma, where atopic conditions often determine clinical courses of asthma.Recently, omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU) with the fixed dose of 300 mg. Although the mechanisms underlying the actions of omalizumab in CSU are not fully clarified, nearly 90% of patients with CSU showed a complete or a partial response to omalizumab treatment. Furthermore, omalizumab is just approved for the treatment of severe Japanese cedar pollinosis (JC) based on the successful results of an add-on study of omalizumab for inadequately controlled severe pollinosis despite antihistamines and nasal corticosteroids. For proper use of omalizumab to treat severe JC, co-administration of antihistamines is necessary, while patients should meet the criteria including strong sensitization to Japanese cedar pollen (≥class 3) and poor control under standard treatment.In the management of severe allergic diseases using omalizumab, issues including cost and concerns about relapse after its discontinuation should be overcome. At the same time, possibilities for application to other intractable allergic diseases should be considered.     

What is new in antiimmunoglobulin E asthma therapy.

Omalizumab, a recombinant humanized monoclonal antibody, is the first therapeutic agent specifically targeting immunoglobulin E (IgE). It has been investigated extensively in the treatment of patients with allergic diseases and is approved in the United States for the treatment of patients with moderate-to-severe persistent asthma. In this setting, omalizumab reduced the frequency and incidence of asthma exacerbations and asthma control was well maintained, even though patients significantly reduced their dose of inhaled corticosteroid. Importantly, omalizumab has been shown to reduce asthma exacerbations in high-risk patients (e.g., with previous intubation and hospitalization) and to reduce the level of severe asthma exacerbations (those resulting in emergency treatment and hospitalization). Responder analysis shows that omalizumab provides the greatest benefit in patients with more severe asthma, and this has been confirmed by recent studies establishing the efficacy of omalizumab in patients whose asthma is poorly controlled despite receiving the best standard care in medication. Omalizumab also has proved to be effective in patients with seasonal and perennial allergic rhinitis and to improve quality of life for patients with asthma or rhinitis. As expected with a systemic anti-IgE agent, omalizumab was shown to be effective in the treatment of patients with concomitant asthma and allergic rhinitis. The efficacy of omalizumab in a range of allergic diseases reaffirms the importance of IgE in the pathogenesis of these conditions and establishes the potential benefit to be obtained by inhibiting IgE, especially in patients with more severe and comorbid allergic diseases.     

奥马珠单抗治疗儿童中重度难治性过敏性哮喘的研究进展

难治性过敏性哮喘是指使用高剂量吸入皮质类固醇(含或不含其他控制性药物)治疗,病情仍得不到控制的、较为顽固的过敏性哮喘。作为重组人源化IgE单克隆抗体的奥马珠单抗,是目前唯一被授权应用于6～18岁中、重度难治性过敏性哮喘患儿的生物制剂。其对血清游离IgE具有高度特异性,能有效阻断IgE与肥大细胞、嗜碱粒细胞等炎症细胞膜表...     

Development of Assay for Determining Free IgE Levels in Serum from Patients Treated with Omalizumab

BackgroundOmalizumab, a monoclonal anti-IgE antibody, is currently indicated for the treatment of moderate-to-severe allergic asthma. To measure active IgE levels in sera from patients treated with omalizumab, the IgE subfraction in complex with omalizumab should be eliminated from total IgE, and free IgE levels can then be determined. With the aim of therapeutic monitoring for anti-IgE therapy, we developed a new ELISA for free IgE.MethodsWe used recombinant human soluble FcεRIα as a capture antigen and a biotinylated polyclonal anti-IgE antibody for detection. Using the newly developed ELISA, we measured the serum free IgE levels weekly in four asthmatic patients after their first omalizumab injection. We also measured the serum free IgE levels in 54 patients treated with omalizumab for over 4 weeks.ResultsThis assay was technically robust, the mean recovery rate in serum was 93.16% ± 5.34%. For all patients, omalizumab treatment significantly reduced serum free IgE levels prior to the second omalizumab injection. To maintain the benefit of omalizumab, serum free IgE concentrations should be < 50 ng/ml. However, in 14 of 54 patients treated with omalizumab for over 4 weeks, serum free IgE concentrations measured by our ELISA were > 50 ng/ml.ConclusionsOur data suggest that the measurement of free IgE levels using our newly developed ELISA would be useful for monitoring serum free IgE levels during omalizumab therapy.     

Efficacy and safety of omalizumab in an Asian population with moderate-to-severe persistent asthma

Background and objective:   The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma.
Methods:   Japanese patients (20–75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study.
Results:   Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min ( P  = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab ( P  = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group.
Conclusions:   Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.