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BACKGROUND: 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. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients

What is known and objective Omalizumab is effective as an add-on drug to treat severe persistent allergic asthma. However, delayed hypersensitivity reactions to omalizumab may deprive patients of its use. Rapid subcutaneous desensitization could be a solution. Case description A 61-year-old man developed a delayed allergy to omalizumab after the first injection. A 14-step desensitization procedure was applied to the patient and was successful. What is new and conclusion Delayed hypersensitivity reactions to omalizumab are rare, but they may cause the interruption of drug usage. Desensitization to omalizumab could be a possible solution.

Background/Aims Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. Methods This 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. Results Of 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). Conclusions Omalizumab 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 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.

Objectives: The aim of this study was to assess the stability of the effectiveness of omalizumab as add-on treatment in 11 patients with severe persistent allergic asthma followed for 4 years. Secondary outcomes were safety and economic impact, in terms of use of healthcare resources. Methods: This retrospective study was designed to analyse a series of patients with severe allergic asthma treated with omalizumab. Patients were initially enrolled as part of the CIGE025A2425 international multicentre clinical trial. At the end (week 32), 11 responsive patients went on to complete the study and continued omalizumab treatment until June 2010. The monitoring visits coincided with the timescales planned for administering the drug and for the follow up. To estimate the economic impact, the PRE–POST treatment comparison was obtained by comparing the annual pretreatment costs with an annual average of the 4-year posttreatment period costs Results: After 4 years, 81.8% of patients showed a good/excellent Global Evaluation of Treatment Effectiveness scale score and 81.2% showed an excellent increase (>1.5) in the Asthma Quality of Life Questionnaire score. The average forced expiratory volume in one second (FEV1) at 4 years was 75.3% compared with the predicted normal value for each patient, with a net increase ( p = 0.009) compared with baseline FEV1 values (58.6%). The frequency of serious exacerbations dropped by 94.7% compared with the pretreatment period, while mild–moderate exacerbations fell by 41.8%. A reduction in costs was observed for hospital admissions (97.3%), visits to emergency department (ED) (97.5%) and mild–moderate exacerbations (84%). The average cost reduction of concomitant drugs remained at 36%. Conclusions: This study confirms the effectiveness and reliability of omalizumab over the long term, while providing an excellent safety profile. The additional cost due the use of omalizumab was offset by the medium- and long-term savings associated with the reduction in hospital admissions and access to ED.

Summary Background In this study we compare the Omalizumab treatment modality in the dynamics of cell apoptosis regulating molecules in both severe persistent asthma patients who had no other any allergic disease, newly diagnosed patients with allergic asthma, and healthy volunteers. Material/Methods Severe persistent allergic asthma patients were subjected to measurement of serum soluble TRAIL (TNF-related apoptosis-inducing ligand) levels during the active disease phase and the stable phase which occurred 4 months after Omalizumab treatment. Serum sTRAIL concentrations were measured by a solid phase sandwich enzyme-linked immunosorbent assay. Concentration levels were compared with those of age- and sex-matched newly diagnosed patients with allergic asthma, and healthy controls. All assays were carried out in duplicate. Total serum IgE levels, antinuclear antibody (ANA), rheumatoid factor (RF), hepatitis markers, C3, C4 and eosinophil levels were evaluated in all patients. Results ANA, RF, hepatitis markers were negative in all patients. Complement 3 and 4 levels were normal in all patients. Prick tests in all patients were detected in mite and grass allergy. These results correlated with specific IgE. There were no differences between the healthy controls, newly diagnosed allergic asthma patients, and non-treated severe persistent allergic asthma patients during the active phase. Interestingly, the levels in variances of the patients who had the effective omalizumab treatment were significantly lower than the healthy controls, while the mean values were not statistically significant. Conclusions Our study gives a different perspective on severe persistent allergic asthma and omalizumab treatment efficacy at the cell apoptosis-linked step by the serum sTRAIL levels.

Patients with asthma who have persistent symptoms despite treatment with inhaled steroids and long-acting beta agonists are considered to have severe asthma. Omalizumab is a monoclonal antibody directed against IgE, which is used as an add-on treatment for patients who have severe persistent allergic asthma.The aim of this study was to assess the clinical benefit and healthcare utilisation of patients who responded to omalizumab therapy and to establish an overall cost implication.This was an observational retrospective cohort study designed to investigate the effect of omalizumab on exacerbations of asthma before and after 6 months of treatment in Irish patients.Centres who had treated patients with severe allergic asthma for the 6 months prior and post omalizumab treatment were audited with a standardised assessment tool. Sixty-three (32 male) patients were studied. In the 6 months prior to omalizumab 41 of 63 (66%) had been hospitalised, and this fell to 15 of 63 (24%), p0.0001 in the 6 months after treatment was started. Hospital admissions reduced from 2.4 ± 0.41 to 0.8 ± 0.37 and the mean number of bed days occupied was reduced from 16.6 ± 2.94 to 5.3 ± 2.57 days, p0.001. The number of oral corticosteroid doses used fell from 3.1 ± 0.27 to 1.2 ± 0.17, p0.001. The overall cost saving per omalizumab responder patients for 6 months waseuro834.Six months therapy with omalizumab reduced the number of bed days, the number of hospitalisations and the use of oral corticosteroids compared to the 6 months prior to commencement. Despite the cost of the additional therapy there were overall savings in health costs.

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.

Background: Omalizumab is a humanized monoclonal anti-IgE antibody developed for the treatment of IgE-mediated diseases, including asthma. The aim of the study was to determine the effect of omalizumab treatment on changes in RANTES in exhaled breath condensate and other inflammatory markers in patients with persistent severe asthma. Methods: The study was conducted on a group of 19 patients with severe persistent allergic asthma treated with conventional therapy (according to GINA 2006) and with or without omalizumab (9 vs. 10 patients). Changes in inflammatory parameters [RANTES in exhaled breath condensate, exhaled nitric oxide, blood eosinophil count and serum eosinophil cationic protein (ECP)] were measured before and after 16 weeks of therapy. Results: Omalizumab-treated patients showed a statistically significant decrease in the concentrations of RANTES in exhaled breath condensate, exhaled nitric oxide (FENO), serum ECP, and blood eosinophil count compared with patients with conventional therapy after 16 weeks of treatment. In this group of patients, statistically significant correlations were revealed between the decrease in RANTES and a decrease in FENO and between the decrease in FENO and a decrease in ECP or blood eosinophil count after omalizumab therapy. Conclusions: Our results confirmed that during anti-immunoglobulin E therapy with omalizumab in patients with severe persistent allergic asthma, RANTES expression is decreased. This process in turn could lead to a limitation of airway inflammation and could be essential for the beneficial effect of anti-IgE therapy with omalizumab.

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.

Rationale: Omalizumab, an anti-IgE monoclonal antibody, is indicated in adults with severe persistent allergic asthma. Exhaled molecular markers can provide phenotypic information in asthma. Objectives: Determine whether adults with severe asthma on omalizumab (anti-IgE + ) have a different breathprint compared with those who were not on anti-IgE therapy (anti-IgE - ) as assessed by eNoses and gas chromatography/mass spectrometry (GC/MS) (breathomics). Methods: This was a cross-sectional analysis of the U-BIOPRED adult cohort. Severe asthma was defined by IMI-criteria [Bel, Thorax 2011]. Anti-IgE + patients were on a regular treatment with s.c. omalizumab (150-375 mg) every 2-4 weeks. Exhaled volatile compounds trapped on adsorption tubes were analysed by a centralized eNose platform (Owlstone Lonestar, two Cyranose 320, Comon Invent, Tor Vergata TEN), including a total of 190 sensors, and GC/MS. Recursive feature elimination (http://topepo.github.io/caret/rfe.html) was used for feature selection and random forests, more robust to overfitting, for classification. Results: 9 anti-IgE + (females/males 2/7, age 52.6±16.3 years, mean±SD, 1/2/6 current/ex/nonsmokers, pre-bronchodilator FEV 1 70.6±21.1% predicted value) and 30 anti-IgE - patients (18/12 females/males, age 53.2±14.2 years, 0/16/14 current/ex/nonsmokers, pre-bronchodilator FEV 1 59.6±30.7% predicted value) were studied. Accuracy of classification is shown in Table 1. Conclusions: Preliminary results suggest that breathomics can distinguish between anti-IgE + and anti-IgE - severe asthma patients.

The objective of this study was to investigate the suitability of recoveryELISA as a method to monitor treatment with therapeutic antibodies using the example of omalizumab. The recoveryELISA is a newly developed immunoassay technology that measures three parameters in one test: the free level of antigen, the level of therapeutic antibody and the specific dose-response interaction which represents the actual activity of the drug. A retrospective and observational analysis was performed on 197 serum samples from 17 patients (13 ± 4 years of age) with severe persistent allergic asthma who received add-on treatment with omalizumab. The mean omalizumab serum level during antibody therapy was 59 ± 45 µg/mL; the kit’s upper detection limit of 140 µg/mL was exceeded in 27 samples. Antibody concentrations between 50 and 140 µg/mL were found in 64 samples. Independent of the omalizumab dosage, nearly all measurements were in a range of absolute saturation as regards the IgE binding rate. Almost complete binding of IgE with a recovery of added labelled IgE of

Background The appropriate dose and frequency of omalizumab in patients with severe asthma was determined in clinical trials based on body weight (kg) and baseline IgE (IU/mL). However, in clinical practice a conversion chart promoted by stakeholders is used for dose determination. Purpose To assess the correlation between omalizumab´s estimated dose calculated from the formula used in pivotal clinical trials (PCT) and prescribed omalizumab dose in clinical practice. We also aimed to analyse the effectiveness of omalizumab based on FEV modifications from baseline. Material and methods Asthmatic patients treated with omalizumab up to July 2015 were evaluated retrospectively. Demographic data (gender and age), body weight, posology (dose and frequency), duration of treatment, baseline and current IgE level, and baseline and current FEV were recorded. Omalizumab estimated dose was calculated according to the PVT formula at baseline: 0.016*weight*IgE (UI/mL) every 4 weeks or 0.008*weight*IgE (UI/mL) every 2 weeks. For patients treated with omalizumab for 3 or more years current weight and IgE was used instead of baseline data to assess omalizumab´s estimated dose. Also, to analyse the effectiveness of treatment, we calculated the difference in FEV from baseline. Statistical analysis were performed using SPSS15. Results 60 patients met the inclusion criteria. 68.3% were female and mean age was 51.8 years (range 16–80). Mean FEV improvement from baseline was 9.69% (range -25%-51.1%). This meant that 56.9% of patients developed an improvement in FEV but 25% had worsening FEV and in 18.3% of patients these data were missing. Comparison between the prescribed dose and estimated dose from the PCT formula showed a concordance of doses in only 20% of cases. Based on these data, 46.3% of patients would benefit from omalizumab dose reduction. Also, 36.7% of patients had a lower prescribed dose than omalizumab’s estimated dose based on the PCT formula. Nevertheless, 61.1% of these patients would not need an increase in dose based on FEV improvement from baseline. Conclusion We found a great discrepancy between estimated omalizumab dose by the PCT formula and the prescribed omalizumab dose in clinical practice. By using the formula we optimised the efficiency of treatment with omalizumab. No conflict of interest.

Background There is no data available to adequately explain the alterations in total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide concentrations in severe persistent asthma and newly diagnosed allergic asthma patients. In the study below we have examined changes in total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide levels in severe persistent asthma and newly diagnosed allergic asthma patients and the association(s) between these variables. Methods The first group of patients included 6 male and 8 female subjects with severe persistent asthma, having a mean age of 42.4 years. A second group of subjects consisted of 14 newly diagnosed allergic asthma patients with a mean age of 43.8 years. All patients were followed in our clinic, and were evaluated by clinical status. A third group of 14 age-sex matched healthy controls were also included. Serum samples were collected and stored at –70 until use for the determination of total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide concentrations. Serum IgE levels, ANA, RF, hepatitis markers, C3, C4 and eosinophil levels were evaluated in all patients. All assays were carried out in duplicate. Results Total antioxidant capacity levels of Group IB, group II and group III were lower than the IA group. Total antioxidant capacity levels of groups II and III were higher than in group IB. Hydrogen peroxide concentrations in group IB were lower than in group IA, while concentrations in group II were higher than in group IB. The malondialdehyde concentration of group IB was lower than in all other groups. The malondialdehyde concentration of group III was higher than all other groups. The malondialdehyde concentration of group II was lower than in group III. The total nitric oxide level of group IB was lower than all other groups. The total nitric oxide level of group III was higher than all other groups, while that of group II was higher than for both groups IA/IB. Conclusions To monitor the omalizumab treatment efficacy in the severe allergic asthma patients; total antioxidant capacity, hydrogen peroxide, malondialdehyde and total nitric oxide concentrations might be new markers.

Background Oral corticosteroids (OCS) are commonly administered in patients with severe persistent allergic asthma. Despite their efficacy, they are associated with a wide variety of adverse events. The eXpeRience registry was set up to investigate real-world outcomes among patients receiving omalizumab for the treatment of uncontrolled allergic asthma. Here, we present the effect of omalizumab treatment on OCS use. Methods eXpeRience was a 2-year, multinational, non-interventional, observational registry of patients receiving omalizumab for uncontrolled allergic asthma. OCS use (proportion of patients on maintenance OCS, mean total daily OCS dose and change in status of OCS therapy) was assessed at baseline, 16 weeks, and 8, 12, 18, and 24 months after the initiation of omalizumab. Response to omalizumab was assessed using the physician’s Global Evaluation of Treatment Effectiveness (GETE) at approximately Week 16. Safety data were also recorded. Results A total of 943 patients (mean age, 45 years; female, 64.9%) were enrolled in the registry, 263 of whom were receiving maintenance OCS at baseline. The proportion of patients taking maintenance OCS was markedly lower at Months 12 (16.1%) and 24 (14.2%) than at baseline (28.6%; intent-to-treat population). GETE status was determined in 915 patients receiving omalizumab: 64.2% were responders (excellent or good response), 30.7% were non-responders (moderate, poor or worsening response); 5.1% had no assessment. The frequency of serious adverse events was comparable to that seen in controlled trials of omalizumab. Conclusions Omalizumab use is associated with an OCS-sparing effect in patients with uncontrolled persistent allergic asthma in the real-world setting.

Method 20 pediatric (12 male and 8 female) patients, with mean age of 8.5 having severe persistent allergic asthma, with recurrent exacerbations and on oral/IV steroids, prospectively received Omalizumab 150mg/300mg, depending on IgE & body weight for 6 month to 1 year,at B.R.Singh Hospital, Kolkata. Number of exacerbations, total dose of oral Steroids, use of rescue medications, ICS/LABA dose used were recorded at the baseline, 24 weeks, end of treatment and on 6 month follow up (between February 2011 and August 2012) and statistically analyzed.