Search

In February 2024, omalizumab was approved by the U.S. Food and Drug Administration for the treatment of food allergy, based on data from the landmark phase 3 clinical trial, Omalizumab as Monotherapy and as Adjunct Therapy in Children and Adults (OUtMATCH). In this Rostrum, OUtMATCH investigators share their perspectives on the trial results, the implications for translation into daily practice, and on remaining gaps in the field. The study met its primary and key secondary end points, demonstrating a large effect size in multiallergen desensitization compared with placebo; yet there were some participants who did not respond, and the percentage of responders tolerating all 3 food allergens was lower than that for single foods. Clinicians are likely to have many questions about appropriate patient selection, monitoring for treatment responsiveness, and how to manage off-label considerations such as dietary incorporation or cotreatment with oral immunotherapy. Additional research is needed to answer these remaining questions and ensure that the translation of omalizumab in real-world practice leads to high-quality outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: Research and regulatory approval for pediatric uses of prescription drugs often lag years after adult approvals, during which time substantial off-label use of medications in children can occur. We evaluated whether US Food and Drug Administration (FDA) regulatory actions affected the pediatric use of omalizumab, a biologic drug used to treat asthma., Methods: In this serial cross-sectional study, we identified quarterly cohorts of children (0-18 years) with moderate-to-severe asthma within two large national claims databases of those with commercial insurance and Medicaid from 2003 to 2019. Using an interrupted time-series analysis, we fit segmented linear regression models to identify changes in the incidence of omalizumab use in 6-11-year-old children compared with 12-18-year-olds after two time points: (1) 2009Q3 when an FDA advisory committee voted against use for 6-11-year-old children and (2) 2016Q2 when FDA expanded omalizumab's labeling to include 6-11-year-old children., Results: We identified 9298 new pediatric omalizumab users (84% Medicaid). Among 6-11-year-old children, the incidence of omalizumab use did not change following the FDA's initial review of evidence in 2009 and increased after 2016 Q2 FDA approval for this age group in both Medicaid (58 per 100 000 children with asthma, 95% confidence interval [CI] 27-89, p < 0.001) and commercial insurance (57 per 100 000, 95% CI 21-94, p = 0.003) compared with 12-18-year-old children., Conclusions: The use of omalizumab among asthmatic children aged 6-11 years remained steady after FDA advisory committee concerns in 2009 and increased after FDA expanded the indication to include this population in 2016. Additional market incentives may help to ensure the timely generation of evidence and regulatory approval of medications for children., (© 2024 John Wiley & Sons Ltd.)

Background: Biologic modifiers targeting type 2 (T2) airway inflammation are effective in reducing asthma exacerbation. However, real-world and comparative effectiveness studies remain limited., Objective: To examine and compare the real-world impact of anti-T2 asthma biologics., Methods: In this retrospective, new user cohort study, we used the MarketScan, a Commercial Claims and Encounters Database, to identify adult patients with asthma who began to receive an anti-T2 biologic agent (anti-IL-5s, dupilumab, or omalizumab). We examined the influence of the biologic class on asthma exacerbation by comparing the average number of asthma exacerbation 1 year before and after biologic initiation. We conducted multivariable regression analyses to compare the effectiveness of these asthma biologics on reducing the incidence of asthma exacerbations within 18 months of the initial administration of biologics while controlling for demographic variables, comorbidities, and asthma severity., Results: We identified 5,538 asthma patients who were new to taking an anti-T2 biologic [mean age [±SD], 45.6 (12.78) years; 65.8% female). Asthma biologics reduced asthma exacerbation by 11% to 47%, particularly among patients with two or more asthma exacerbations in the year preceding biologic initiation (31% to 65% reduction). Biologics were especially effective in reducing asthma-related hospitalizations (44.6% to 60%). After adjusting for baseline demographics, asthma medication, and comorbidities, dupilumab was associated with a lower estimated mean number of asthma exacerbation per year and lower adjusted odds ratio for developing an asthma exacerbation relative to other biologics (50% to 80% less likely)., Conclusions: Anti-T2 asthma biologics reduced asthma exacerbation in real-word settings. Evidence supports growing literature reporting that dupilumab might have a more favorable impact on asthma exacerbation relative to other asthma biologics., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

A substantial portion of asthma and nasal polyps (NPs) share a common pathogenesis, which includes type 2-mediated inflammation. Distinct endotypes and phenotypes characterizing asthma and chronic rhinosinusitis have been identified. With emerging evidence describing pathophysiology, novel targets for biologic monoclonal antibody treatments have been developed. There are currently six biologic therapies approved by the US Food and Drug Administration to treat asthma, including omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab, three of these-omalizumab, mepolizumab, and dupilumab-are also approved for NPs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two prevalent nasal diseases where both type 2 inflammation and immunoglobulin E (IgE) may play important roles. Although they can exist independently or comorbidly, subtle but important differences exist in immunopathogenesis., Objective: To summarize current knowledge of pathophysiological roles of B lineage cells and IgE in AR and CRS with nasal polyps (CRSwNP)., Methods: Searched PubMed database, reviewed AR and CRSwNP-related literature, and discussed disease diagnosis, comorbidity, epidemiology, pathophysiology, and treatment. Similarities and differences in B-cell biology and IgE are compared in the 2 conditions., Results: Both AR and CRSwNP have evidence for pathological type 2 inflammation, B-cell activation and differentiation, and IgE production. However, distinctions exist in the clinical and serological profiles at diagnosis, as well as treatments utilized. B-cell activation in AR may more frequently be regulated in the germinal center of lymphoid follicles, whereas CRSwNP may occur via extrafollicular pathways although controversies remain in these initial activating events. Oligoclonal and antigen-specific IgE maybe predominate in AR, but polyclonal and antigen-nonspecific IgE may predominate in CRSwNP. Omalizumab has been shown efficacious in treating both AR and CRSwNP in multiple clinical trials but is the only Food and Drug Administration-approved anti-IgE biologic to treat CRSwNP or allergic asthma. Staphylococcus aureus frequently colonizes the nasal airway and has the ability to activate type two responses including B-cell responses although the extent to which it modulates AR and CRSwNP disease severity is being investigated., Conclusion: This review highlights current knowledge of the roles of B cells and IgE in the pathogenesis of AR and CRSwNP and a small comparison between the 2 diseases. More systemic studies should be done to elevate the understanding of these diseases and their treatment.

Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future., (© 2022 The Author. Parasite Immunology published by John Wiley & Sons Ltd.)

Chronic spontaneous urticaria (CSU) is characterized by recurring wheals that last 6 weeks or longer without an identifiable cause. The estimated point prevalence of CSU worldwide is 1%. Furthermore, it has a significant impact on quality of life in both adults and pediatric patients and their families. Although it is most often a self-limited disease, some patients have urticaria refractory to first-line treatment: second-generation H1 antihistamines. In these patients, the use of targeted monoclonal antibodies is necessary. While omalizumab is the only Food and Drug Administration-approved monoclonal antibody for CSU, others, including ligelizumab, dupilumab, benralizumab, and several orally administered Bruton's tyrosine kinase inhibitors, are also promising therapeutics for reducing the morbidity of CSU. Novel therapies, among others discussed here, are rapidly being developed with new trials and therapeutics being released nearly monthly. Thus, we performed a scoping literature review of randomized controlled trials studying targeted therapies for CSU. We also discuss the pathophysiology, diagnosis, prognosis, and future research directions in CSU., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare the outcomes of real-world patients who would have been eligible for asthma biologics to those who would not have been eligible., Methods: We used data from the OptumLabs Data Warehouse (OLDW) to categorize patients into eligible and ineligible groups based on clinical trials ( n  = 19 trials) used for Food and Drug Administration (FDA) approval. We then compared the change in the number of asthma exacerbations before and after biological initiation between the two groups., Results: The percentage of people who would have been eligible for asthma biologic clinical trials ranged from 0-10.2%. The eligible group had a greater reduction in number of asthma exacerbations compared to the ineligible group based on eligibility criteria from 1 omalizumab trial (1.52, 95% CI 1.25, 1.8 in eligible vs. 0.47, 95% CI 0.43, 0.52 in ineligible) and from 1 dupilumab trial (1.6, 95% CI 0.92, 2.28 in eligible vs. 0.52, 95% CI 0.38, 0.65 ineligible). Notably, 15 of the 19 trials had fewer than 11 eligible people, limiting additional comparisons., Conclusions: Fewer than 1 in 10 people in the United States treated with asthma biologics would have been eligible to participate in the trial for the biologic they used. Where comparisons could be made, trial eligible people have a greater reduction in exacerbations., Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.2010749 .

Background : Omalizumab has been demonstrated to be effective in treating chronic spontaneous urticaria (CSU) and was FDA approved for this indication in 2014. Previous work has shown that access to injectable biologics varies across US counties. In the present study we evaluate geographic and temporal trends in the utilization of omalizumab in the Medicare population by dermatologists, with its use by allergists and pulmonologists as comparators. Methods : We analyzed year-over-year trends in omalizumab utilization across geographic regions using the Medicare Provider Utilization and Payment Data: Part D files. Results : Utilization of omalizumab by dermatologists increased rapidly after its FDA approval, from 0.08 claims/100,000 enrollees totaling $209/100,000 enrollees in 2014 to 1.45 claims/100,000 enrollees totaling $3115/100,000 enrollees in 2017. Nonetheless, prescribing dermatologists were present in only 2.8% (95% Confidence Interval (CI): 2.0%-3.9%) and 0.2% (95% CI: 0.0%-0.5%) of metropolitan and non-metropolitan counties, respectively, in 2017, demonstrating limited availability, especially in non-metropolitan counties. Similarly, prescribers of any specialty were available in 32.9% (95% CI: 30.2%-35.6%) and 3.8% (95% CI: 3.1%-4.8%) of metropolitan and non-metropolitan counties, respectively, in 2017. Conclusions : Our data suggest that despite increasing omalizumab utilization, there remains a lack of access across many counties, particularly in non-metropolitan regions. Efforts to expand omalizumab prescriber accessibility in these counties may improve outcomes for patients with CSU., (Copyright ©2022, Yale Journal of Biology and Medicine.)

Background: Asthma in older adults is associated with high rates of morbidity and mortality; similarly, asthma can be severe enough among younger adults to warrant disability benefits. Reasons for poor outcomes in both groups of patients may include discontinuation and lack of adherence to controller therapies., Objective: To examine characteristics and treatment patterns of US Medicare patients initiating omalizumab for asthma, and factors associated with its discontinuation and adherence., Methods: A retrospective claims database analysis of Medicare beneficiaries with asthma initiating omalizumab treatment was carried out. The primary outcomes were omalizumab discontinuation (gap in use ≥90 days) and adherence (proportion of days covered ≥0.8) over a 12-month follow-up. Multivariable regressions were used to examine factors associated with omalizumab discontinuation and adherence., Results: Of the 3058 Medicare patients initiating omalizumab for asthma (mean age, 62.7 years), 36.9% discontinued omalizumab and 60.6% were adherent. Discontinuation rates were 32.7% and 42.8%, and adherence rates were 65.4% and 53.9%, for disabled and older Medicare patients, respectively. Patients aged 65 to 69 years and 70 to 74 years had significantly lower odds of discontinuation (odds ratios [95% CI], 0.66 [0.46-0.93] and 0.62 [0.43-0.89], respectively) and higher odds of adherence than did patients aged 80 years or older. Compared with patients receiving low-income subsidy, patients not receiving low-income subsidy had lower odds of discontinuation (0.66 [0.52-0.83]) and higher odds of adherence (1.52 [1.20-1.93]). Greater numbers of preindex evaluation and management physician visits and comorbid rhinitis were associated with lower odds of discontinuation and higher odds of adherence., Conclusions: More than 60% of Medicare patients with asthma continued and were adherent to omalizumab over a 12-month follow-up. Patient age, low-income subsidy status, and the numbers of evaluation and management physician visits were among factors associated with treatment adherence and discontinuation., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Uncontrolled asthma is associated with considerable clinical burden and costs to payers and patients. US economic models evaluating biologics using data from clinical trials demonstrate high incremental cost-effectiveness ratios (ICERs), but the cost-effectiveness based on real-world treatment patterns is unknown. This analysis used real-world evidence to assess the cost-effectiveness of adding omalizumab to standard of care (SOC). Methods: A Markov model was applied to track patients' health states in 2-week cycles, comparing costs and treatment effects of SOC alone versus SOC + omalizumab over a lifetime (US payer perspective). Outcomes included exacerbation events, life years, quality-adjusted life years (QALYs), total costs, and an ICER. Patient characteristics, exacerbations, patient-reported outcomes, and work productivity were derived from the real-world PROSPERO (Prospective Study to Evaluate Predictors of Clinical Effectiveness in Response to Omalizumab) study. Published literature informed mortality, exacerbation-related disutility, and unit costs. Sensitivity analyses assessed model robustness. Results: Over a lifetime horizon, omalizumab was associated with an increase of 2.0 QALYs at a cost of $US 148,319 in patients with uncontrolled asthma (ICER of $75,319/QALY gained) and a reduction in exacerbations of 6.0 events/patient. Accounting for responder status improved the ICER ($70,505/QALY); incorporating indirect costs further reduced the ICER. One-way and multivariate sensitivity analyses confirmed that the base case outcome was robust to variation in inputs. Conclusions: Based on real-world outcomes, omalizumab may be cost-effective for uncontrolled asthma from the US payer perspective. Including broader evidence on treatment discontinuation, caregiver burden, and oral corticosteroid reduction from real-world studies may better reflect the effects and value of omalizumab for all healthcare stakeholders.

Objective: Five biologic therapies have FDA-approved indications for difficult-to-control asthma. The clinical trials that proved the efficacy and safety of these biologics were often similar in their inclusion criteria, study designs, and endpoints. Many of these trials have been reanalyzed post hoc to identify subsets of subjects considered to be enhanced responders. As a result, keeping up with the literature and deciding on the most appropriate biologic for our patients has become increasingly difficult. This review summarizes and compares trial designs, patient cohorts, and study results of the major trials involving these therapies., Data Sources: Included are basic science articles, online Food and Drug Administration (FDA) applications, and all the published reports of phase II and phase III clinical trials for FDA-approved asthma biologics., Study Selections: Included are the major phase II and phase III clinical trials of 5 asthma biologics., Results: Because of variations in inclusion criteria and natural variations in enrolled cohorts, the baseline clinical traits and severity of study populations in asthma biologic trials differed significantly, which is important because baseline annualized exacerbation rates and blood eosinophilia are both strong predictors of a biologic's success. Notwithstanding, the trial results, when considered together, can help guide care providers in choosing the most appropriate biologic for our patients., Conclusion: Understanding the details and differences in asthma biologic trial designs, patient cohorts, and in study results will help care providers make more informed decisions when choosing a biologic. We are hopeful this review will serve as a reference to care providers for this purpose., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

Background: Utilization trends of omalizumab, a first-in-its-class asthma biologic approved in 2003 for individuals not controlled by inhaled corticosteroids (ICSs), may reveal lessons in patient selection., Objective: To describe utilization patterns for omalizumab since its introduction in 2003, with a focus on patient-level characteristics of patients for whom omalizumab was initiated., Methods: Using a large US database of administrative claims, we identified privately insured and Medicare Advantage beneficiaries with asthma between 2003 and 2015. Characteristics of incident (no omalizumab use in the previous 12 months) and prevalent users of omalizumab for asthma were described and omalizumab use trends graphed. A comparison cohort (1:5 matching proportion) of nonomalizumab users was compared with incident omalizumab users on demographic characteristics, medication adherence (medication possession ratio [MPR]) for ICSs and/or ICS/long-acting β-agonist (ICS-LABA), exacerbation frequency, and asthma control in the 6 months before omalizumab initiation., Results: We identified 7,658 prevalent and 3,399 incident omalizumab users. Omalizumab incidence peaked in the second quarter of 2004 at 0.65 per 1,000 individuals with asthma, whereas prevalence peaked in the fourth quarter of 2006 at 3.22; as of fourth quarter 2015, rates were 0.14 and 1.96, respectively. In the 12 months before omalizumab initiation, 72.5% had low adherence (MPR ≤ 0.75) and 48.6% had very low adherence (MPR ≤ 0.5) to ICSs and/or ICS-LABA. In the period 2003 to 2015, the mean number of exacerbations in the 12 months before incident use ranged from 1.50 to 2.11 and the proportion that had poor asthma control (≥3 rescue inhalers dispensed) ranged from 54% to 67%. Incident omalizumab users were less likely to have good asthma control than the matched cohort of nonusers (adjusted odds ratio, 0.53 [0.48-0.59])., Conclusions: Omalizumab use for asthma has been gradually decreasing following a peak shortly after its market availability. Many omalizumab users have low or very low adherence rates for ICSs and/or ICS-LABA in the 12 months before omalizumab initiation., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to examine patient characteristics, treatment patterns, and exacerbations among patients with asthma newly treated with omalizumab., Methods: Data for this study were obtained from administrative claims and medical records. The index date was the date of the first claim for omalizumab. All patients had ≥12 months of continuous health plan eligibility before and after the index date. Demographic and clinical characteristics were obtained 12 months before the index date. Treatment patterns of asthma medications, including omalizumab, and asthma exacerbations were evaluated in the preindex and postindex periods., Findings: The study included 1564 patients. Asthma-related medication use decreased from the preindex to the postindex periods (oral corticosteroids, 83.3%-66.4%, P < 0.001; inhaled corticosteroids [ICSs], 33.1%-26.8%, P < 0.001; long-acting β 2 -adrenergic agonists [LABAs], 6.6%-5.2%, P = 0.009; ICS-LABA combination, 69.3%-64.3%, P < 0.001; leukotriene modifiers, 67.8%-59.7%, P < 0.001). The proportion of patients with any asthma exacerbations decreased by 33.6% (66.6%-44.2%, P < 0.001). Notably, the relative decreases in hospitalization and emergency department exacerbations were 79.3% and 72.2%, respectively. A total of 930 patients (59.5%) discontinued omalizumab treatment during the entire postindex period (maximum, 3400 days [approximately 9 years]), with 353 (38.0%) restarting omalizumab treatment., Implications: In this real-world analysis, patients newly initiating omalizumab therapy for allergic asthma used fewer concomitant asthma medications, while experiencing significant reductions in asthma exacerbations, especially hospitalization- and emergency department-specific exacerbations, from pre- to post-omalizumab treatment initiation periods., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Omalizumab was approved for the treatment of chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) in the United States in March 2014., Objective: This study sought to describe real-world omalizumab use, in the United States, in a large cohort of patients with CIU/CSU., Methods: Patients with CIU/CSU (ages ≥12 years) initiated on omalizumab (index date) with ≥12 months of pre- and postindex data were identified in the an insurance claims data base (January 1, 2013, to July 31, 2016). Treatment patterns, including the dosing regimen and continuous use of omalizumab (no gaps for ≥60 days), were described during the 12-month postindex follow-up period., Results: A total of 1546 patients (mean ± standard deviation [SD] ages, 44 ± 14.5 years; 73.1% women) were identified. Most of the patients (84.5%) were initiated on omalizumab 300-mg dose; 90% maintained the initial dose, 7.5% had a dose increase, and 4.6% had a dose decrease. The mean ± SD omalizumab treatment duration was 9.1 ± 3.8 months, the mean ± SD number of omalizumab administrations was 8.3 ± 4.8, and the mean ± SD administration frequency was 44 ± 29 days. A proportion of the patients continuously treated with omalizumab for 6, 9, and 12 months was 67.3, 54.8, and 47.4%, respectively. Among the patients who discontinued omalizumab for ≥3 months (39.8%), 21% restarted the treatment after a mean ± SD of 4.4 ± 1.3 months. The proportion of patients who used other CIU/CSU-related medications decreased pre- to postindex (94.8 to 81.1%), with the highest decrease observed in oral corticosteroids (75.7 to 49.9%)., Conclusion: In this large real-world study, the majority of the patients with CIU/CSU were initiated on a 300-mg omalizumab dose and treated without titration up or down for 9 months on average. Most of the patients were continuously treated with omalizumab for ≥6 months, and one-fourth of the patients who discontinued treatment resumed it. Moreover, compared with baseline levels, the use of other CIU/CSU-related medications was lower after omalizumab initiation, with the most prominent decrease observed in oral corticosteroids.

Background: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials., Objective: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy., Methods: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab., Results: A higher saEPI was associated with an exacerbation in both the GBT alone (P < .001; area under the curve, 0.76) and the GBT + omalizumab group (P < .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups., Conclusions: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.)