Severe Persistent Allergic Asthma Research Articles

Asthma improvement in patients treated with dupilumab for severe atopic dermatitis.

Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD). We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year. A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity. Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma.

Background/AimsOmalizumab is the first biologic known to be effective in patients with severe allergic asthma.MethodsThis study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma.ResultsOf the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001).ConclusionsOmalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients<18years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. Of the 484 patients included, 101 (20.9%) reached 6years of treatment. The mean±standard deviation number of exacerbations decreased during the first year of treatment (7.9±6.6 to 1.1±2.0, P<.001) and remained likewise for up to 6years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Treatment Benefit with Omalizumab in Children by Indicators of Asthma Severity

Greater severity in childhood asthma negatively impacts functioning and quality of life. Omalizumab is effective in children aged 6 years or older with moderate to severe persistent asthma, but predicting responsiveness in severe disease requires further study. To assess response to omalizumab treatment among children using indicators of asthma severity. Post hoc analyses of randomized placebo-controlled studies of omalizumab (Inner-City Anti-IgE Therapy for Asthma [ICATA], IA05, and Preventative Omalizumab or Step-up Therapy for Fall Exacerbations [PROSE]) stratified by body mass index, eosinophil count, fractional exhaled nitric oxide levels, and baseline severity indicators (baseline percent predicted FEV1, previous hospitalizations, asthma exacerbations). Poisson regression analysis examined exacerbation rate reductions for body mass index, biomarkers, and severity indicators. Children aged 6 to 11 years in IA05 (N= 576; 56% white, 17% black, 26% other/missing), ICATA (N= 237; 55% black, 43% Hispanic), and PROSE (N= 342; 59% black, 35% Hispanic) were included. Trends indicative of greater exacerbation rate change ([omalizumab - placebo]/placebo) were observed for low baseline lung function (IA05 percent predicted FEV1: <90%, 36% reduction, 95% CI,-53.3 to-13.5; ≥90%, 22% reduction, 95% CI,-52.1 to 27.5), previous hospitalizations (ICATA: 46% reduction with, 95% CI,-69.7 to-3.9; 24% reduction without, 95% CI,-48.1 to 10.3), frequent baseline exacerbations (IA05: ≥3, 42% reduction, 95% CI,-60.4 to-14.1; <3, 20% reduction, 95% CI,-45.2 to-15.9), and high baseline eosinophil count (IA05: ≥300 cells/μL, 39% reduction, 95% CI,-56.4 to-14.7; <300 cells/μL, 5% reduction, 95% CI,-40.6 to 52.1). Omalizumab reduces exacerbations in children with moderate to severe persistent allergic asthma, and may provide greater benefit in children with more severe asthma subtypes.

The effectiveness of omalizumab in the control of severe uncontrolled asthma in Latin America. An exploratory systematic review and meta-analysis

Omalizumab is effective in the treatment of severe persistent allergic asthma that is not controlled with long-acting beta-agonists/ high-dose inhaled corticosteroids. To conduct a systematic exploratory review and meta-analysis of studies with omalizumab in Latin America. A search of real-life studies on the effectiveness of omalizumab in asthma control conducted in Latin America was carried out. The average of the aggregate effectiveness of omalizumab in asthma control (Pooled Analysis) was estimated by using a random effects model. Nine open uncontrolled observational studies were identified; these studies included a total of 1 118 patients with severe uncontrolled asthma. The average of the estimated aggregate effectiveness of omalizumab in the good control of severe asthma was of 80.6 % in children and 78.9 % in adults. The average of the estimated aggregate effectiveness of omalizumab in the control of severe asthma in both children and adults in Latin America was over 78 %. Randomized controlled studies are required in order to establish the efficacy and effectiveness of omalizumab in the control of severe asthma and in the different subgroups by level of eosinophils.

Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a review

&#x0D; &#x0D; &#x0D; &#x0D; Increased asthma severity is not only associated with enhanced recurrent hospitalization and mortality but also with higher social costs.Several cases of asthma are atopic in nature, with the trigger for acute asthma attacks and chronic worsening of inflammation being allergens inducing an immune, IgE mediated response.&#x0D; Anti-inflammatory 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 biological engineered, humanized recombinant monoclonal anti-IgE antibody developed for the treatment of allergic diseases and with clear efficacy in adolescent and adult patients with 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 has demonstrated to be a very useful treatment of atopic asthma, improving quality of life of patients with severe persistent allergic asthma that is inadequately controlled by currently available asthma medications. Several trials have demonstrated that this therapy is well tolerated and significantly improves symptoms and disease control, reducing asthma exacerbations and the need to use high dosage of inhaled corticosteroids.&#x0D; &#x0D; &#x0D; &#x0D;

IL-33, IL-25, and ECP Levels were Decreased in Severe Persistent Allergic Asthma Patients with the Anti-IgE (Omalizumab) Treatment

IL-33, IL-25, and ECP Levels were Decreased in Severe Persistent Allergic Asthma Patients with the Anti-IgE (Omalizumab) Treatment

Assessment of efficacy of Anti-IgE (Omalizumab) therapy in patients with severe allergic asthma in a tertiary care hospital of Eastern India

Introduction: Immunoglobulin E dependent mechanisms play an important role in the development of airway inflammation in allergic asthma. Atopic patients with severe asthma frequently have poorly controlled disease. Many have poor asthma control despite intensive treatment. Severe allergic asthma patients frequently treated with oral corticosteroids and therefore may develop serious side-effects. Anti-IgE antibody had been used in severe persistent allergic asthma in Western countries. However, its long-term efficacy in patients in India has not been reported. Objective: To assess the efficacy of anti IgE therapy in patients with severe allergic asthma. Method: 30 (16 male and 14 female) patients, with mean age of 49 having severe persistent allergic asthma, with recurrent exacerbations and on oral/IV steroids, received Omalizumab 150mg/300mg/450 mg for 1 year. Total dose of oral Steroids, use of rescue medications, changes in lung function (FEV1) were recorded at the baseline, 16 weeks & at end of the treatment (52 weeks) and then analyzed. Results: Significant reduction observed in total oral steroid use at 16 week & at 52 weeks. -10.5mg (p<0.003) & 22.5mg respectively. Use of rescue medications decreased by -7.90 puffs(p- <0.001) at 16 weeks and by -13.67 puffs (13.67 (p -<0.001) at 52 weeks. Improvements in lung Function (FEV1) observed with a tune of 700 ml. from Baseline after 52 weeks therapy. Conclusion: Use of anti-IgE antibody for 1 year is well tolerated and led to an overall significant improvement in patients with severe persistent allergic asthma.

USE OF OMALIZUMAB IN FOUR-YEAR-OLD WITH SEVERE PERSISTENT ALLERGIC ASTHMA

Introduction Omalizumab is approved in patients with moderate to severe persistent allergic asthma older than 6 years of age. We report use of omalizumab for the treatment of uncontrolled asthma in a 4-year-old. Case Description Patient is a 4-year-old boy who presented with uncontrolled, severe, persistent asthma despite use of high dose inhaled corticosteroid and long acting beta agonist therapy. In addition to requiring systemic steroids as an outpatient, he had hospitalizations for an asthma exacerbation every month. His IgE was 636 U/ML and eosinophil count was 350/cmm. He was too young to appropriately perform a pulmonary function test. His allergen specific IgE testing showed multiple environmental allergen sensitivities. After starting the treatment with omalizumab, frequency of exacerbations requiring systemic steroids significantly decreased and he has not required hospitalization. Discussion Omalizumab, a monoclonal antibody against IgE, is approved for moderate to severe allergic asthma in children six years and older. There is difficulty in managing children who meet criteria for omalizumab treatment but due to age limit they are unable to qualify for this treatment. To our knowledge, there is limited evidence in the literature for omalizumab treatment in children less than six years of age. After starting omalizumab, the patient has significant improvement in quality of life and required less frequent use of systemic steroids. Omalizumab should be considered in certain circumstances in children younger than 6 years of age for severe persistent asthma unresponsive to conventional treatment to improve quality of life and for its steroid sparing effects.

Cost Effectiveness of Pharmacological Treatments for Asthma: A Systematic Review.

The objective of this article was to summarize the findings of all the available studies on alternative pharmacological treatments for asthma and assess their methodological quality, as well as to identify the main drivers of the cost effectiveness of pharmacological treatments for the disease. A systematic review of the literature in seven electronic databases was conducted in order to identify all the available health economic evidence on alternative pharmacological treatments for asthma published up to April 2017. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. A total of 72 studies were included in the review, classified as follows: medications for acute asthma treatment (n = 5, 6.9%); inhaled corticosteroids (ICS) administered alone or in conjunction with long-acting β-agonists (LABA) or tiotropium for chronic asthma treatment (n = 38, 52.8%); direct comparisons between different combinations of ICS, ICS/LABA, leukotriene receptor antagonists (LTRA), and sodium cromoglycate for chronic asthma treatment (n = 14, 19.4%); and omalizumab for chronic asthma treatment (n = 15, 20.8%). ICS were reported to be cost effective when compared with LTRA for the management of persistent asthma. In patients with inadequately controlled asthma taking ICS, the addition of long-acting β-agonist (LABA) preparations has been demonstrated to be cost effective, especially when combinations of ICS/LABA containing formoterol are used for both maintenance and reliever therapy. In patients with uncontrolled severe persistent allergic asthma, omalizumab therapy could be cost effective in a carefully selected subgroup of patients with the more severe forms of the disease. The quality of reporting in the studies, according to the CHEERS checklist, was very uneven. The main cost-effectiveness drivers identified were the cost or rate of asthma exacerbations, the cost or rate of the use of asthma medications, the asthma mortality risk, and the rate of utilization of health services for asthma. The present findings are in line with the pharmacological recommendations for stepwise management of asthma given in the most recent evidence-based clinical practice guidelines for the disease. The identified reporting quality of the available health economic evidence is useful for identifying aspects where there is room for improvement in future asthma cost-effectiveness studies.

Monitoring of omalizumab therapy in children and adolescents.

Background: Omalizumab is a successfully implemented supplementary therapy for improving asthma control in children aged 6 years and older with severe persistent allergic asthma. The dosage of omalizumab depends on body weight and IgE level, yet no parameter has been established to guide dosage changes during therapy. Clinical studies in patients with allergic asthma or allergic rhinitis revealed a clinically relevant improvement by using omalizumab leading to concentrations of free serum IgE reported to be lower than 50 ng/ml. Therefore, only the question concerning the concentrations of free IgE used in a therapy with omalizumab is regarded of clinical importance, while total IgE (free and omalizumab-bound IgE) increases during treatment. Patients and methods: Ten patients, 8 to 17 years of age, received therapy with omalizumab due to severe allergic asthma. In addition, the patients had pronounced rhinoconjunctivitis, food allergy, insect sting allergy, and/or neurodermitis. The total IgE in the serum was measured in the patients 3 – 6 months before each omalizumab injection as a potential progress parameter (Sandwich-Immunoassay ADVIA Centaur). Results: Six months after beginning of the therapy with omalizumab, a significant decrease of the total IgE concentration was found, in comparison to the baseline values (p < 0.003). In all patients the tolerability of omalizumab was very good: there was a reduction in the frequency of the asthma exacerbations and rescue medications. All patients reported a clearly improved quality of life. Conclusions: A general increase in IgE was not observed in any of the children we treated with omalizumab. Apart from the development of routine assays to determine free serum IgE levels, the significance of the total serum IgE as a suitable control of an omalizumab therapy should be further investigated in controlled studies with regard to sensitivity and specificity. In order to only administer the lowest necessary dose of omalizumab especially in children and adolescents, the establishment of laboratory parameters (free IgE and/or total IgE) to adequately monitor the therapy is urgently needed. Patients undergoing an omalizumab therapy require medical supervision at close intervals.

No evidence for IgE receptor FcεRI expression on bronchial epithelial cells of asthmatic patients

Immunoglobulin E (IgE) plays an important role in the pathogenesis of asthma and anti-IgE therapy was approved for treating patients with severe persistent allergic asthma. The exact target sites of anti-IgE therapy are not well characterized; however, it has been proposed that the therapeutic effects of anti-IgE come from its intervention in the airway remodeling process. To gain insights on how anti-IgE therapy improves asthma symptoms, we aimed to validate the expression of FceRI on airway epithelial cells and demonstrate its role in airway remodeling. The expression of FceRI was measured (1) in situ in bronchial biopsy tissues of asthmatic and control subjects using immunohistochemistry and (2) in vitro in primary bronchial epithelial cells obtained from asthmatic subjects, at baseline and after treatment with human IgE, using qPCR and flow cytometry. FceRI expression in situ was detected only in a very small number of cells in the epithelium of bronchial biopsies of asthmatic and control subjects. In vitro measurement revealed no expression of the receptor both at baseline and after stimulation with IgE. The release of transforming growth factor—beta (TGF)-β and thymic stromal lymphopoietin (TSLP) were examined by ELISA in bronchial epithelial cells after crosslinking of IgE. No significant differences in TSLP and TGF-β protein levels were detected between stimulated and unstimulated cells. Hence, our data conclusively indicate that bronchial epithelial cells have negligible expression of functional high affinity receptor for IgE. Taken together, anti-IgE therapy is very likely to exert its therapeutic effects via other structural cell types.

Targeted therapy in severe asthma today: focus on immunoglobulin E.

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard “one size fits all” approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

Longterm clinical outcomes of omalizumab therapy in severe allergic asthma: Study of efficacy and safety

Omalizumab has been shown to be an effective add-on therapy for patients with uncontrolled severe persistent allergic asthma. There has been a steady accumulation of evidence on the long-term effectiveness of omalizumab; however, data on real-life outcomes beyond one year of treatment is limited. In this study, we report on long-term outcomes of omalizumab treatment. We collected data from our severe asthma registry on hospitalisations, exacerbations, corticosteroid sparing, asthma control, lung function, biomarkers and side effects, to determine if the benefit was sustained and treatment was safe on the long term. Forty-five patients [mean age 44.9 years (range 19–69), females 37/45 (82%), mean duration of omalizumab treatment = 60.7 ± 30.9 months (range 23–121) were included in the analysis. We observed a reduction in the annual acute asthma related hospital admissions for the total population from 207 at baseline to 40 on treatment (80.7% reduction), whilst the per patient annual hospitalisations were reduced from a mean of 4.8 to 0.89 post-omalizumab treatment (p < 0.00001). There was a 76.7% reduction in daily mean maintenance OCS dose (prednisolone equivalent) from 25.8 mg (n = 43) to 6.0 mg (p < 0.0001), associated with clinically significant improvement in asthma control questionnaire (ACQ) from mean score of 4.1 (range 3.7–4.7) to 2.27 (range 0.5–4.1) p < 0.0001. The mean % predicted FEV1 has improved from 59.2% at baseline to 75.7% on treatment (p = 0.001). There was a statistically non-significant reduction in median peripheral blood eosinophils (PBE) from 300 cells/μl (range 40–1050) at baseline to 175 cells/μl (range 0–1500) post-treatment (p = 0.068), and statistically significant reduction of median fraction exhaled nitric oxide (FeNO) level from 37 parts per billion (range 12–178) to 24 ppb (range 7–50) (p = 0.0067). The work/school missed days were reduced in 17/19 patients who were at employment or school. The overall safety profile of the treatment seemed acceptable and was consistent with published experience. In conclusion, results from this real-life study demonstrate that improved outcomes in patients with severe allergic asthma are sustained with longer-term omalizumab therapy.

Real-life Efficacy of Omalizumab After 9 Years of Follow-up.

Omalizumab is frequently used as add-on treatment to inhaled corticosteroids (ICS) and long-acting β2-agonists in patients with suboptimal control of severe asthma. Patients with severe asthma will typically require chronic treatment, although due to the limited amount of data available there are still some concerns about the safety and efficacy of long-term therapy with omalizumab. Herein, in an extension of a previous 4-year study, we report disease-related outcomes of 8 patients with severe persistent allergic asthma who have been followed for a total of 9 years in a real-life setting. Both quality of life (QoL) (evaluated using the Juniper Asthma-Related QoL Questionnaire [AQLQ]) and forced expiratory volume in 1 second (FEV1) showed sustained improvement at 9 years. The median values of AQLQ and FEV1 at 4 years were 5.5 and 82.0% compared to 5.9 and 85.5%, respectively, at 9 years, which were all significantly increased from baseline. After 9 years, the mean annual number of severe exacerbations was 0.63 compared to 5 at baseline. There also appeared to be a trend toward use of a lower dose of ICS at longer follow-up times. After 9 years, there were no safety concerns for continued use of omalizumab, and no asthma-related hospitalizations or emergency department visits were documented over the last 5 years. The present analysis is the longest reported clinical follow-up of omalizumab. Long-term maintenance treatment with omalizumab for up to 9 years is associated with continued benefits in reducing symptoms, exacerbations, and medication burden without any safety concerns.

Novel targets of omalizumab in asthma.

Omalizumab is a recombinant humanized anti-IgE monoclonal antibody approved in the US for moderate to severe persistent allergic asthma (severe persistent asthma in the European Union), uncontrolled despite treatment with inhaled corticosteroids and long-acting beta2 agonists. It reduces asthma exacerbations, symptoms, oral corticosteroid doses, and improves quality of life. Omalizumab may have an antiviral effect when used as a preventive therapy for fall exacerbations in children and teenagers. Two proof-of-concept studies have evaluated omalizumab in nonatopic asthma and showed that it is safe and possibly efficacious in some patients. Omalizumab has been successfully studied as add-on to specific immunotherapy in moderate allergic asthma. Its safety in pregnancy has been assessed in the EXPECT registry. Case series also report positive effects in cases of allergic bronchopulmonary aspergillosis, and in nasal disorders frequently associated with asthma. Last, omalizumab may have corticosteroid-sparing effect in a subset of patients with eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome). Recent studies argue in favor of positive effects of omalizumab beyond its current indications in asthma. Well-designed studies are needed in order to demonstrate the safety and efficacy of omalizumab in these possible novel indications.

PRS41 - Estimating The Impact Associated To The Use Omalizumab In The Treatment of Severe Persistent Allergic Asthma In Portugal – Evaluating Outcomes And Treatment Costs Using Real World Data From Portuguese Patients

PRS41 - Estimating The Impact Associated To The Use Omalizumab In The Treatment of Severe Persistent Allergic Asthma In Portugal – Evaluating Outcomes And Treatment Costs Using Real World Data From Portuguese Patients

Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study)

ObjectiveTo describe the impact of omalizumab on asthma management in patients treated as part of normal clinical practice in the UK National Health Service (NHS).DesignA non-interventional, mixed methodology study, combining...

Comparison of allergic asthma patients treated with omalizumab and non-allergic patients treated with continuous oral corticosteroids: results of five year follow-up therapies.

To assess the long-term (5 year) efficacy of omalizumab and systemic corticosteroid therapy in allergic and non-allergic asthma that could not be controlled by step 4 therapy, respectively. This single-center study was based on all consecutive step 4 patients with severe persistent uncontrolled allergic and non-allergic asthma who were given omalizumab and systemic corticosteroid (minimum: 4 mg, maximum: 12 mg, median: 8 mg methyl prednisone), respectively, in 2006-2014 and were followed up for at least 5 years. Asthma control test (ACT), FEV1 and exacerbation rates at initial presentation and 1, 2, and 5 years after step 5 treatment initiation were calculated for both groups. There were 17 and 16 allergic and non-allergic group patients, respectively. Both groups exhibited significant improvements in ACT at the 1st, 2nd, and 5th years relative to baseline (all p< 0.01). The allergic group had significantly better ACTs at 16 weeks, 1 year, and 2 years than the non-allergic group (all p< 0.01). By the 5th year, the exacerbations in the non-allergic group rose significantly by 39.6% (3.3 on average) compared to baseline (2.38 on average, p< 0.001). By contrast, the allergic group continued to have significantly fewer exacerbations at the 5th year (77.1% fewer relative to baseline, p< 0.001). However, 47% of the allergic group patients still presented with one exacerbation in the 5th year. Adding omalizumab to step 5 therapy improved the control of severe persistent allergic asthma. However, nearly half of the patients in both groups presented at least one exacerbation in the 5th year.

Treating IgE-mediated diseases via targeting IgE-expressing B cells using an anti-CεmX antibody.

Targeting the IgE pathway is a clinically validated strategy for treating IgE-mediated diseases. Omalizumab, an anti-IgE antibody, which binds to free IgE and prevents the binding of IgE to FcεRI on mast cells and basophils has been approved for severe persistent allergic asthma and chronic spontaneous (idiopathic) urticaria. The therapeutic efficacy of anti-IgE has also been reported in allergic rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, anaphylaxis, and others. Anti-CεmX, which binds to membrane-bound IgE (mIgE) on IgE-switched B cells, lyses mIgE-expressing B lymphoblasts and prevents the allergen-induced generation of IgE-producing plasma cells, offers an alternative mechanism of intervening with the IgE inflammatory pathway. Because anti-CεmX does not bind to free IgE, it can modulate the IgE pathway regardless of the serum IgE levels in treated patients. These unique pharmacologic mechanisms potentially enable anti-CεmX to provide different clinical utilities from anti-IgE and serve as a therapeutic and a prophylactic in some IgE-mediated diseases, which are not adequately treated with current medicine.