Reduced Effectiveness of Anti-IgE Treatment Among Adults with Severe Asthma with Older Age of Asthma Onset: Results from the CHRONICLE Study.

Purpose: Younger age of asthma onset (AAO) has been associated with an allergic phenotype, whereas eosinophilic phenotypes have been associated with older AAO. In randomized trials, biologic efficacy among adults with severe asthma (SA) has varied by age at asthma onset. To determine whether these associations observed in trials apply to real-world outcomes, this study examined biologic effectiveness by AAO and biologic class in a large, real-world cohort. Patients and methods: CHRONICLE is an ongoing, real-world study of US adults with subspecialist-treated SA receiving biologics, maintenance corticosteroids, or who are uncontrolled on high-dosage inhaled corticosteroids with additional controllers. Patients enrolled between February 2018 and February 2022 who initiated a biologic for SA and had complete data for analysis were included. A locally estimated scatterplot smoothing (LOESS) analysis was used to plot the relationship between percentage exacerbation rate reduction and AAO by biologic class. Results: Of 578 patients with complete data, 198, 149, and 231 were diagnosed with asthma at age <18, 18-39, and ≥40 years, respectively. Across subgroups, patients were predominantly White (72-78%), female (67-73%), and commercially insured (54-71%). In the LOESS analysis, exacerbation rate reductions were similar for anti-IgE and anti-IL-5/5R and anti-IL-4R subgroups with younger AAO, but the exacerbation rate reduction diminished for patients with older AAO receiving anti-IgE therapy, particularly with asthma onset age ≥40 years. Conclusion: Clinicians should consider age of onset in biologic treatment decisions, given reduced effectiveness of omalizumab in patients with asthma onset at age ≥40 years. Clinicaltrialsgov Identifier: NCT03373045.

Immunoglobulin G genetic variation can confound assessment of antibody levels via altered binding to detection reagents.

Objectives: Amino acid variations across more than 30 immunoglobulin (Ig) allotypes may introduce structural changes that influence recognition by anti-Ig detection reagents, consequently confounding interpretation of antibody responses, particularly in genetically diverse cohorts. Here, we assessed a panel of commercial monoclonal anti-IgG1 clones for capacity to universally recognise two dominant IgG1 haplotypes (G1m-1,3 and G1m1,17). Methods: Four commercial monoclonal anti-human IgG1 clones were assessed via ELISAs and multiplex bead-based assays for their ability to bind G1m-1,3 and G1m1,17 IgG1 variants. Detection antibodies were validated against monoclonal IgG1 allotype standards and tested for capacity to recognise antigen-specific plasma IgG1 from G1m-1,3 and G1m1,17 homozygous and heterozygous SARS-CoV-2 BNT162b2 vaccinated (n = 28) and COVID-19 convalescent (n = 44) individuals. An Fc-specific pan-IgG detection antibody corroborated differences between hinge- and Fc-specific anti-IgG1 responses. Results: Hinge-specific anti-IgG1 clone 4E3 preferentially bound G1m1,17 compared to G1m-1,3 IgG1. Consequently, SARS-CoV-2 Spike-specific IgG1 levels detected in G1m1,17/G1m1,17 BNT162b2 vaccinees appeared 9- to 17-fold higher than in G1m-1,3/G1m-1,3 vaccinees. Fc-specific IgG1 and pan-IgG detection antibodies equivalently bound G1m-1,3 and G1m1,17 IgG1 variants, and detected comparable Spike-specific IgG1 levels between haplotypes. IgG1 responses against other human coronaviruses and influenza were similarly poorly detected by 4E3 anti-IgG1 in G1m-1,3/G1m-1,3 subjects. Conclusion: Anti-IgG1 clone 4E3 confounds assessment of antibody responses in clinical cohorts owing to bias towards detection of G1m1,17 IgG1 variants. Validation of anti-Ig clones should include evaluation of binding to relevant antibody variants, particularly as the role of immunogenetics upon humoral immunity is increasingly explored in diverse populations.

Comparison of the General Characteristics of Patients with Severe Asthma Who Switched from Omalizumab to Mepolizumab versus Patients Who Responded to Omalizumab Treatment: A Real-Life Study.

INTRODUCTION: Severe asthma is characterized by frequent recurrent airway symptoms and exacerbations, and these affect the quality of life. Biological agents can be used in the treatment of patients with severe asthma if the disease cannot be controlled with standard controller treatment. The aim of this study was to compare the clinical characteristics and laboratory data of patients with severe asthma who were switched from omalizumab to mepolizumab and patients with severe asthma who responded to omalizumab. METHODS: The clinical characteristics and laboratory data of patients with severe asthma who responded to omalizumab and switched from omalizumab to mepolizumab were compared retrospectively. RESULTS: Evaluation was made of a total of 79 patients, including 64 omalizumab responders and 15 who switched to mepolizumab from omalizumab. After omalizumab and mepolizumab treatment, the annual number of asthma attacks, the use of oral corticosteroid (OCS), the annual number of hospitalizations, and the eosinophil count significantly decreased (omalizumab: p < 0.001, p < 0.001, p < 0.001, p < 0.001, respectively; mepolizumab: p = 0.001, p = 0.001, p = 0.002, p = 0.001, respectively). After omalizumab treatment, the increase in forced expiratory volume in 1 s (FEV1) (%) and asthma control test (ACT) score were determined to be statistically significant (p < 0.001, p < 0.001, respectively). After mepolizumab treatment, the increase in ACT score was significant (p = 0.003). Drug allergy, chronic sinusitis with nasal polyps (CRSwNP), regular use of OCS, and high baseline eosinophil count (cells/µL) were associated with poor response to omalizumab treatment (odds ratio [OR] = 7.86, p = 0.003; OR = 52.92, p < 0.001; OR = 10.16, p = 0.004; OR = 0.99, p = 0.004, respectively). House dust mite sensitivity and high baseline FEV1 (%) were associated with good response to omalizumab treatment (OR = 0.29, p = 0.041; OR = 1.06, p = 0.03, respectively). The blood eosinophil count had diagnostic value in predicting the nonresponsiveness to omalizumab treatment (area under the curve [AUC]: 0.967, p < 0.001, cut-off: 510). CONCLUSION: A high pretreatment eosinophil count, concomitant CRSwNP, a history of drug allergy, and regular OCS use may be associated with poor response to omalizumab treatment in patients with severe asthma. Depending on the treatment response, treatment switching can be applied between biological agents. The results of the current study should be supported by multicenter studies.

Characterization methods for studying protein adsorption on nano-polystyrene beads.

This work is dealing with the use of polystyrene (PS) nanoparticles as substrates for bioanalytical specific interactions. Different techniques were used for the accurate characterization of the PS nanoparticles of 100 nm and 196 nm before coating them with a layer of antibodies against immunoglobulins of type E (aIgE), giving to the particle a specific functionality. The formation of the aIgE adsorbed layer was monitored using centrifugal particle separation (CPS) and centrifugal field flow fractionation (CF3) experiments, which allowed to determine the size changes and the adsorbed mass. Particle sizes were also measured with DLS, used both as stand-alone instrument and coupled to CF3 (CF3-DLS). The complementary information obtained from the CPS and CF3-DLS measurements allowed the estimation of the density of the aIgE shell. The proteins immobilized at the surface fully retained their activity, as proven by the reactions between the functionalized PS-aIgE particles and immunoglobulins of type E (IgE) dispersed in suspensions prepared on purpose.

Step-up and step-down treatments for optimal asthma control in children and adolescents.

OBJECTIVE: To review therapeutic options for stepwise management of pediatric asthma in the context of this population's unique needs such as potential effects of asthma, treatments, or both on growth and psychosocial development, and caregiver involvement. DATA SOURCES AND STUDY SELECTION: We conducted PubMed searches to identify relevant articles then reviewed resultant articles, guidelines for asthma management in children, and articles from personal files. RESULTS: Stepwise management of asthma, similar to adults, is recommended for children in current global and US guidelines. Treatment may be stepped up or stepped down temporarily or long-term based on response over time. Inhaled corticosteroids remain the recommended treatment for persistent childhood asthma and any potential small effects on growth are considered relatively minor compared with their benefit. Controller medication options for patients <18 years old are limited, especially for Global Initiative for Asthma Steps 2-5. The long-acting antimuscarinic antagonist tiotropium (Steps 4/5, patients aged ≥12 years) and in certain circumstances (Step 5), anti-immunoglobulin E (aged ≥6 years) and interleukin-5 antibodies (aged ≥12 years) are newer treatment options. Tiotropium is indicated in the United States and Europe for patients ≥6 years old. Stepping down treatment, which is recommended but infrequently practiced, can maintain symptom control and minimize adverse events while substantially reducing costs. Patient education and better monitoring remain important for self-management and optimum outcomes. CONCLUSION: A need exists to target individual treatment goals for children with asthma by using step-up and step-down approaches to maximize treatment benefits and minimize potential adverse effects.

Description of Baseline Characteristics of Pediatric Allergic Asthma Patients Including those Initiated on Omalizumab.

BACKGROUND: Indication of omalizumab in the United States was recently extended to include pediatric (6-11 years) uncontrolled moderate-to-severe allergic asthma patients. OBJECTIVE: The purpose of this study was to describe baseline characteristics of this population from a real-world dataset. METHODS: Allergic asthma patients and uncontrolled moderate-to-severe allergic asthma patients, aged 6-11 years, were identified in the Allergy Partners Network Electronic Medical Records (2007-2016). The index date for allergic asthma patients was the latest between the second asthma-related visit and the allergic status confirmation. Uncontrolled moderate-to-severe allergic asthma patients were stratified into omalizumab-exposed (index date) or omalizumab-unexposed (index date randomly generated) groups. Characteristics were evaluated during the 12-month preindex period. RESULTS: A total of 5806 allergic asthma, 37 omalizumab-exposed, and 2620 omalizumab-unexposed patients were selected (mean age approximately 9 years). Allergic asthma and omalizumab-unexposed patients were predominantly white (70.2% and 61.2%) whereas the majority of omalizumab-exposed were African Americans (62.2%). Mean immunoglobulin E was 782.0 IU/ml in allergic asthma patients (available in 2.2%), 1134.4 IU/ml in omalizumab-exposed (available in 100.0%), and 746.1 IU/ml in omalizumab-unexposed (available in 3.1%). Allergic asthma patients were less severe than omalizumab-exposed and omalizumab-unexposed based on the forced expiratory volume in 1 s as a percentage of predicted value (FEV1% predicted) and the Childhood Asthma Control Test (C-ACT). FEV1% predicted was below normal (<80%) in 42.4% of omalizumab-exposed and 39.1% of omalizumab-unexposed patients, also 63.6% of omalizumab-exposed and 46.7% of omalizumab-unexposed had uncontrolled asthma (C-ACT score <20). In African American omalizumab-exposed patients, FEV1% predicted was below normal in 47.6% and 55.0% had uncontrolled asthma. CONCLUSIONS: In a real-world setting, pediatric patients with uncontrolled moderate-to-severe allergic asthma have a significant disease burden as shown by high rates of poor lung function, disease control, and symptoms. Currently available treatments could help improve disease management in this population.

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.

A comparative study showing the potency of anti-C3d and anti-immunoglobulin G in polyspecific anti-human globulin using fresh and cryopreserved red blood cells.

BACKGROUND: The antiglobulin test is used to determine red blood cells (RBCs) having surface-bound immunoglobulin G (IgG) and/or complement (C3b, C3d, C4b, and C4d) free in serum or attached to antigens on RBCs. In such circumstances, the quality of the anti-human globulin (AHG) which is used in routine cross-match/indirect agglutination test plays a vital role in blood transfusion medicine. For potency testing of polyspecific AHG, it is recommended by the Food and Drug Administration and the Centre for Biologics Evaluation and Research to use fresh O +ve RBCs within 1 hr of collection for sensitization with anti-C3d. AIM AND OBJECTIVE: Freshly collected red cells were cryopreserved and stored at a temperature of -70°C for 30 days. These cells were then sensitized with C3d and IgG after deglycerolization. Their viability was checked by potency testing using polyspecific AHG-containing anti-C3d and anti-IgG. MATERIALS AND METHODS: Anonymous left over fresh whole blood samples were collected from the Indian Red Cross Society, New Delhi, with CPDA as an anticoagulant, and the samples were treated within 1 h of collection. ABO and Rh (D) phenotyping was performed by test tube method. RBCs and plasma from the same donor were used throughout the study. RESULTS: In this comparative study, fresh RBCs (O +ve) maintained their viability after cryopreservation and were also found to be suitable for sensitization with C3d and IgG. The potency of polyclonal AHG did not differ significantly with fresh RBCs and cryopreserved RBCs for 30 days. CONCLUSION: This result suggests that the sensitization of fresh RBCs with IgG and C3d is not affected by using cryopreserved cells for 30 days.

A novel route to prepare a multilayer system via the combination of interface-mediated catalytic chain transfer polymerization and thiol-ene click chemistry.

Herein, we have designed a novel multilayer system composed of poly(methyl methacrylate) [poly(MMA)] brush, biotin, streptavidin and protein-A on a silicon substrate to attach onanti-immunoglobulin G (anti-IgG). poly(MMA) brush with vinyl end-group was first synthesized by the interface-mediated catalytic chain transfer polymerization. The brush was then modified with cysteamine molecules to generate the polymer chains with amine end-group via a thiol-ene click chemistry. The amine end-groups of poly(MMA) chains were also modified with biotin units to ensure selective connection points for streptavidin molecules. Finally, a multilayer system on the silicon substrate was formed by using streptavidin and protein-A molecules, respectively. This multilayer system was employed to attach anti-IgG molecules in a highly oriented manner and provide anti-IgG molecular functional configuration on the multilayer. High reproducibility of the amount of anti-IgG adsorption and homogeneous anti-IgG adsorption layer on the silicon surface could be provided by this multilayer system. The multilayer system with protein A may be opened the door for designing an efficient immunoassay protein chip.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

AIM: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS: Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

Use of omalizumab in the treatment of chronic urticaria.

BACKGROUND: Omalizumab is indicated to treat chronic spontaneous urticaria (CSU) refractory to antihistamines. We aim to describe the experience of our department in the treatment of CSU with omalizumab. MATERIALS AND METHODS: Retrospective review of the clinical records of patients. RESULTS: Six patients (5 females, median age 33 years) treated with omalizumab for a median of 17.5 months were evaluated. All patients had improvement of symptoms after the first dose. In one case, the treatment was suspended after 7 months, but in 9 weeks there was recurrence of symptoms. The main side effect was headache in the drug administration's day. Currently, all patients maintain therapy with omalizumab and are clinically stable. CONCLUSION: Omalizumab proved to be an effective and safe drug for the treatment of patients with refractory CSU.

Ethnic sensitivity assessment of pharmacokinetics and pharmacodynamics of omalizumab with dosing table expansion.

A three-part license expansion for omalizumab (Xolair(®)), humanized anti-IgE antibody, was recently made in Japan for paediatric use, additional higher doses and revised dosing frequency in allergic asthma. The dosing level and frequency of omalizumab are guided by a dosing table based on the total serum IgE and bodyweight. Nonlinear mixed-effect pharmacokinetic (PK) and pharmacodynamic (PD) modeling and simulation techniques described the binding between omalizumab and its target IgE. The population PKPD analysis was conducted using data from the nine studies included originally in the European application of dosing table expansion together with three Japanese clinical studies to assess the influence of the ethnicity. Statistically significant differences between the ethnic groups were detected. These were small, within or close to bioequivalence criteria. The model described the primary pharmacology in Caucasian and Japanese patients, both adult and paediatric, with simulations showing that the interplay between the clearance, volume and binding affinity parameters was such that there was no clinical impact of the Japanese ethnic differences on either drug PK or free IgE suppression and hence the required posology.

Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma.

INTRODUCTION: The real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. METHODS: The methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. RESULTS: Of the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). CONCLUSION: The findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study.

Revision of omalizumab dosing table for dosing every 4 instead of 2 weeks for specific ranges of bodyweight and baseline IgE.

The dosing level and frequency of omalizumab are guided by a dosing table based on total serum immunoglobulin E (IgE) and bodyweight. Using a validated, mathematical simulation model (based on concentration data from 8 studies), we evaluated the impact of a revised omalizumab dosing table (every 4 weeks dosing regimen) on the pharmacokinetic and pharmacodynamic profiles of free and total IgE. Safety analysis, in patients with high levels of exposure to omalizumab, was done using data from the clinical and post-marketing databases. The model accurately predicted observed omalizumab, free and total IgE concentrations. After reaching steady-state, the average increase in exposure was 10%, even for patients with the highest concentrations at the upper 97.5th percentile. Free IgE suppression slightly increased in the initial phase, and slightly reduced at the trough of the dosing cycle, but average suppression remained similar for both regimens. The safety profile of omalizumab was similar for patients receiving higher or lower doses. Thus, doubling the dose of omalizumab, in a subset of patients receiving 225-300 mg of omalizumab (every 2 weeks dosing regimen) can efficiently suppress free IgE without compromising safety or efficacy.

Healthcare Resource Utilization in Patients Receiving Omalizumab for Allergic Asthma in a Real-World Setting.

INTRODUCTION: Inadequately controlled asthma is associated with increased healthcare resource utilization. The eXpeRience registry was initiated to evaluate real-world outcomes in patients receiving omalizumab for uncontrolled persistent allergic asthma. The current analysis of data from the eXpeRience registry focuses on healthcare resource utilization and on absences from work or school. METHODS: The eXpeRience was a 2-year, multinational, non-interventional, observational registry conducted to investigate real-world outcomes among patients receiving omalizumab in accordance with country-specific prescribing criteria for the treatment of uncontrolled persistent allergic asthma. Asthma-related healthcare resource utilization (hospitalizations, emergency room visits or unscheduled-asthma-related doctor visits or interventions) and absences from work or school were assessed pre-treatment (12-month data were collected retrospectively at baseline) and at months 12 and 24 after the initiation of omalizumab treatment. Serious adverse event (SAE) data were also assessed. RESULTS: A total of 943 patients (mean age 45 years; female 65%) were enrolled in the registry. Overall, the mean (standard deviation [SD]) number of asthma-related medical healthcare uses per patient decreased from 6.2 (6.97) during the pre-treatment period to 1.0 (1.96) and 0.5 (1.28) at months 12 and 24, respectively. The mean (SD) number of work or school days missed due to asthma was also lower at months 12 (3.5 [17.28] and 1.6 [4.28], respectively) and 24 (1.0 [4.66] and 1.9 [5.46], respectively) compared with the pre-treatment period (26.4 [49.61] and 20.7 [27.49], respectively). The nature and frequency of SAEs in the eXpeRience registry were comparable to that seen in interventional clinical trials with omalizumab. CONCLUSION: The results of the eXpeRience registry indicate that omalizumab is associated with reductions in healthcare utilization, and in the number of days of absence from work or school, in patients with uncontrolled persistent allergic asthma in the real-world setting. FUNDING: Novartis Pharma AG, Basel, Switzerland.

Correlations between Anti-Mast Cell Autoantibodies and Chronic Idiopathic Urticaria.

BACKGROUND: The etiology of chronic idiopathic urticaria (CIU) is not completely clear. There are a few antibodies were reported to correlate with CIU. OBJECTIVE: To investigate the correlation these antibodies and CIU. METHODS: The autologous serum skin test (ASST) and allergens were performed. Serum levels of immunoglobulin E (IgE), anti-FcεRI and anti-IgE, anti-Helicobacter pylori (HP) antibodies and anti-thyroglobulin antibody (TGAb) were measured in 100 patients with CIU, acute urticaria (AU) and normal controls respectively. RESULTS: Eighty-six percent food or inhalant allergens were detected in AU patients, but no allergens were detected in CIU patients and normal controls. Serum anti-FcεRI antibody and anti-IgE antibody levels were higher in the CIU than that in the AU patients and normal controls (p<0.05, respectively). IgE level was lower in the CIU patients (T=190.00, p< 0.05), but increased in the AU patients (T=226.00, p<0.05) compared with the normal controls. The ASST positive rates in the CIU and the AU patients were 53.4% and 12.6% respectively, but all normal controls were negative. The anti-FcεRI antibody level was higher in the ASST-positive CIU patients than those negative ones (T=101.73, p<0.05). In anti-HP antibody positive and TGAb positive CIU patients, anti-FcεRI antibody positive rate was higher than AU patients (p<0.01) and normal controls (p<0.01). CONCLUSION: The anti-FcεRI and anti-IgE antibodies play a key role in CIU, but anti-HP antibody and TGAb have an indirect correlation with CIU.

Eligibility for treatment with omalizumab in Italy and Germany.

Omalizumab is an add-on therapy for patients with uncontrolled severe allergic asthma. In Europe, patients must fulfil a number of additional criteria to become eligible for omalizumab therapy, creating a challenge for epidemiology studies to quantify the potential patient pool. Thus, and in the absence of robust data, the number of omalizumab-eligible patients has remained unclear. To assess eligible patient numbers, a chart-audit design approach was employed to measure epidemiology variables based on patient-level data. 770 patient charts were reviewed in designated towns in Germany and Italy, in collaboration with >200 primary care physicians (PCPs) and respiratory specialists (RS). This study sample represents >50% and >70% of local RS in these designated towns of Germany and Italy, respectively. Of patient charts evaluated, 4 patients were currently receiving omalizumab. A further 31 patients (12 PCP; 19 RS) were evaluated as omalizumab-eligible (i.e. fulfilled all product label criteria) but were not receiving the drug. Extrapolating to a national level, this yields >6500 eligible patients in Germany, and >3200 in Italy. Furthermore, this study sample revealed a significant number of PCPs treating uncontrolled severe asthma patients without referral to RS; these patients are not consistently evaluated for FEV1, aero-allergen sensitivity, a qualitative understanding of severe exacerbations, and day and night-time symptoms. This study suggests that significant numbers of omalizumab-naïve severe allergic asthma patients in Germany/Italy are eligible for omalizumab therapy. Despite proven benefits in uncontrolled severe allergic asthma, adjunctive omalizumab therapy is underutilized.

Omalizumab in the treatment of chronic urticaria.

Omalizumab is a monoclonal anti-immunoglobulin E antibody currently only approved for use in severe, refractory asthma. In recent years, many authors have reported satisfactory results with omalizumab in patients with difficult-to-treat chronic urticaria. As a result, clinical trials were undertaken to broaden the indication of omalizumab to include chronic urticaria, and the drug was recently cited as a third-line treatment after selective antihistamines at high doses in a consensus document on the treatment of chronic urticaria. In this article our aim is to provide a comprehensive update on the use of omalizumab in the treatment of chronic urticaria. The structure of this biologic agent and its possible mechanisms of actions in this setting will be presented. Treatment strategies and the different dosage regimens used in the series of cases published to date will also be reviewed. Finally, we will discuss the adverse effects that may arise with treatment and the recommended strategies for minimizing the most feared effect, anaphylaxis. Based on the experience of many researchers, omalizumab is emerging as a novel treatment for certain types of spontaneous refractory chronic urticaria and has shown promising results in this setting. The drug has a good safety profile and the main limitation is its high cost.

Anti-IgE na urticária crônica / Anti-IgE in chronic urticaria

A urticária é uma condição frequente; consiste de lesões eritematopapulosas pruriginosas, isoladas ou agrupadas, fugazes, geralmente circulares, podendo variar em forma e tamanho. Convencionalmente, a urticária pode ser dividida, quanto a sua duração, em duas formas: aguda e crônica. Na forma crônica as lesões estão presentes diariamente ou quase diariamente, permanecendo menos de 24 horas na maior parte dos casos, durante um período superior a seis semanas, frequentemente tendo impacto na qualidade de vida. A anti-IgE é um anticorpo monoclonal humanizado aprovado para o uso em asma de difícil controle. Atualmente, várias linhas de evidência indicam que a anti-IgE pode ser benéfica no tratamento da urticária espontânea crônica e física. Neste artigo revisamos as principais e atuais publicações sobre o uso de anti-IgE para o tratamento da urticária crônica refratária aos tratamentos convencionais. Outros estudos ainda são necessários para melhor compreender os mecanismos envolvidos na resposta favorável a esta terapia.

Urticaria is a common condition, consisting of fleeting erythematopapulous pruritic lesions, appearing isolated or grouped, usually circular, but varying in shape and size. Conventionally, hives can be divided into acute and chronic, according to their duration. In the chronic form, lesions are present daily or almost daily, remaining present for less than 24 hours in most cases, over a period longer than 6 weeks, usually with an impact on quality of life. Anti-immunoglobulin E (anti-IgE) is a humanized monoclonal antibody approved for use in difficult-to-control asthma. Currently, several lines of evidence indicate that anti-IgE antibodies can be beneficial in the treatment of chronic spontaneous and physical urticaria. In this paper, we review major and current publications on the use of anti-IgE for the treatment of chronic urticaria refractory to conventional treatment. Further studies are needed to better understand the mechanisms involved in the favorable response of chronic urticaria to this therapy.