Persistent Allergic Asthma Research Articles

The effectiveness of subcutaneous immunotherapy in allergic diseases of children and adults

ObjectivesImmunotherapy is the gradual administration of increasing doses of allergens to reduce or eliminate the patient's adverse clinical response following exposure to these allergens. The goal of the current study was to evaluate the effectiveness of subcutaneous immunotherapy in patients with allergic diseases referred to the Bushehr Asthma and Allergy Clinic, Iran. Materials and methodsPatients with respiratory allergic diseases, who had positive skin prick test, randomly enrolled in this observational study and underwent immunotherapy for one year. To evaluate the efficacy of immunotherapy, two questionnaires were completed for all the patients before and one year after the start of immunotherapy, including the Total Nasal Symptom Score (TNSS) and Asthma Control Test (ACT). ResultsA total of 878 patients with asthma or allergic rhinitis disorder [53.6% (n=471) male and 46.4% (n=407) female] with a median (IQR) age of 28.0 (12.0–35.0) years were randomly enrolled in this observational study. Five hundred forty-nine patients (64.8%) were over 18 years old and 298 patients (33.9%) were under 18 years old, the age of the other patients was not known. The median (IQR) duration of disease was 84.0 (36.0–138.0) months. Rinithis allergy had most frequent than asthma [39.9% (n=350) vs. 22.2% (n=195), respectively] and 218 patients (24.8%) have both of them. After the treatment, 234 patients (54.5%) completely stop and 26.3% patient (n=113) used less than half of the drugs. The mean TNSS (n=259) and ACT (n=186) scores for patients had significant difference before and after immunotherapy [13.64 vs. 5.68, P<0.001; 7.91 vs. 17.43, P<0.001, respectively]. ConclusionThe mean TNSS and ACT score before and after the treatment significantly improved the patients’ symptoms. To conclude, standard immunotherapy can be effective in patients with moderate to severe allergic rhinitis and mild to moderate persistent allergic asthma to reduce clinical symptoms.

Effectiveness of omalizumab across different dosing regimens in patients with moderate-to-severe allergic asthma

For patients with moderate-to-severe persistent allergic asthma, omalizumab is approved for subcutaneous administration according to a recommended dosing table based on weight and total immunoglobulin E (IgE) level. The aim of this analysis was to assess asthma outcomes including quality of life in patients with allergic asthma initiated on omalizumab in the PROSPERO trial; patients were stratified by where their IgE and body weight fell on the approved dosing table. Patient groups were defined as Inside Dosing Table: patients whose IgE and weight fell within the approved dosing table (n = 506); Insufficient Data to Recommend a Dose: patients who fell into the section of the approved dosing table where not enough clinical data were available to make dosing recommendations (n = 72); and Outside Dosing Table: patients who fell outside the approved dosing table due to baseline IgE and/or weight (n = 209). Overall, asthma and quality of life outcomes were improved after omalizumab initiation for both patients who fall within the recommended dosing table or those who fall outside the recommended dosing table. Our results suggest that omalizumab treatment may be effective in a wide range of patients with moderate-to-severe allergic asthma.ClinicalTrials.gov identifier NCT01922037.

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 Immunotherapy on Patients with Bronchial Asthma

Immunotherapy, also known as allergen-specific immunotherapy or desensitization, involves gradually increasing doses of specific allergens to induce immune tolerance and modify the allergic response. The therapy aims to alleviate symptoms, reduce medication usage, and potentially modify the underlying disease process. Several studies have investigated the effects of immunotherapy on asthma patients, providing insights into its clinical efficacy and safety. Research studies have shown positive outcomes of immunotherapy in bronchial asthma. A randomized controlled trial demonstrated significant improvements in asthma symptoms, decreased medication use, and reduced airway hyperresponsiveness in patients who received subcutaneous immunotherapy compared to the placebo group. Another study focusing on children showed improvements in lung function and reduced asthma exacerbations with sublingual immunotherapy. Long-term effects of immunotherapy were explored in a prospective cohort study on adults with moderate-to-severe persistent allergic asthma. The study found sustained improvements in asthma control, reduced rescue medication use, and a de

Physiologically-Based Pharmacokinetic Modeling of Omalizumab to Predict the Pharmacokinetics and Pharmacodynamics in Pediatric Patients.

Omalizumab is widely used in clinical practice; however, knowledge gaps in the dosage of omalizumab for children aged 2-6 years with moderate-to-severe persistent allergic asthma have been identified. The aim of this study was to explore dosing regimens for moderately-to-severely allergic pediatric patients aged 2-6 years. The physiologically-based pharmacokinetic (PBPK) model of omalizumab was developed and verified in adult patients, extrapolated to pediatric patients, and simulated for omalizumab by adding two observation chambers (free IgE and total IgE). The simulation results showed that the fold errors of the predicted and observed values of the area under the curve (AUC) and peak plasma concentration (Cmax ) were between 0.5 and 2.0, and the average folding error and the absolute average folding error values for all concentration-time data points were 1.09 and 1.48, respectively. The PBPK model combined with pharmacokinetic/pharmacodynamic analysis of omalizumab demonstrated that both the model-derived dose and the original dose could control the average free IgE of 2-6-year-old children with moderate-to-severe allergic asthma below 25 ng/mL, and some of the model-derived doses were lower. This conclusion provides a basis for the selection of dosage in clinical practice reference.

Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis

Asthma prevalence and severity have markedly increased with urbanisation, and children in low-income urban centres have among the greatest asthma morbidity. Outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood. We aimed to investigate the associations between regional air pollutant concentrations, respiratory illnesses, lung function, and upper airway transcriptional signatures in children with asthma, with particular focus on asthma exacerbations occurring in the absence of respiratory virus. We performed a retrospective analysis of data from the MUPPITS1 cohort and validated our findings in the ICATA cohort. The MUPPITS1 cohort recruited 208 children aged 6-17 years living in urban areas across nine US cities with exacerbation-prone asthma between Oct 7, 2015, and Oct 18, 2016, and monitored them during reported respiratory illnesses. The last MUPPITS1 study visit occurred on Jan 6, 2017. The ICATA cohort recruited 419 participants aged 6-20 years with persistent allergic asthma living in urban sites across eight US cities between Oct 23, 2006, and March 25, 2008, and the last study visit occurred on Dec 30, 2009. We included participants from the MUPPITS1 cohort who reported a respiratory illness at some point during the follow-up and participants from the ICATA cohort who had nasal samples collected during respiratory illness or at a scheduled visit. We used air quality index values and air pollutant concentrations for PM2·5, PM10, O3, NO2, SO2, CO, and Pb from the US Environmental Protection Agency spanning the years of both cohorts, and matched values and concentrations to each illness for each participant. We investigated the associations between regional air pollutant concentrations and respiratory illnesses and asthma exacerbations, pulmonary function, and upper airway transcriptional signatures by use of a combination of generalised additive models, case crossover analyses, and generalised linear mixed-effects models. Of the 208 participants from the MUPPITS1 cohort and 419 participants from the ICATA cohort, 168 participants in the MUPPITS1 cohort (98 male participants and 70 female participants) and 189 participants in the ICATA cohort (115 male participants and 74 female participants) were included in our analysis. We identified that increased air quality index values, driven predominantly by increased PM2·5 and O3 concentrations, were significantly associated with asthma exacerbations and decreases in pulmonary function that occurred in the absence of a provoking viral infection. Moreover, individual pollutants were significantly associated with altered gene expression in coordinated inflammatory pathways, including PM2·5 with increased epithelial induction of tissue kallikreins, mucus hypersecretion, and barrier functions and O3 with increased type-2 inflammation. Our findings suggest that air pollution is an important independent risk factor for asthma exacerbations in children living in urban areas and is potentially linked to exacerbations through specific inflammatory pathways in the airway. Further investigation of these potential mechanistic pathways could inform asthma prevention and management approaches. National Institutes of Health, National Institute of Allergy and Infectious Diseases.

The "real-world" effectiveness and safety of omalizumab in patients with uncontrolled persistent allergic asthma in Slovakia: a subgroup analysis of the eXpeRience study.

Omalizumab was proven to be effective and safe in patients with moderate-to-severe allergic asthma. However, there is no direct evidence of the benefits of add-on omalizumab in real-life practice in the Slovakian population. This subgroup analysis assessed the real-life effectiveness and safety of omalizumab in Slovakian patients with severe allergic asthma enrolled in the eXpeRience registry. Patients who commenced omalizumab 15 weeks prior to inclusion were assessed for the physicians' global evaluation of treatment effectiveness (GETE), exacerbation rate, asthma symptoms, lung function, oral corticosteroid (OCS) use, rescue medication, hospitalizations, and school/work absenteeism at 16 weeks and 12 and 24 months. Of 204 patients, 159 (77.9%) completed 2-year follow-up. As per GETE, 69.5% of patients treated with omalizumab achieved excellent/good response at 16 (±1) weeks. The proportion of patients with no severe clinically significant asthma exacerbations increased from 17.3% at pre-treatment to 82.4% and 92.0% at months 12 and 24, respectively. Maintenance OCS use was reduced to 17.0% and 15.3% of patients at 12 and 24 months, respectively, compared with 34.7% at baseline (BL). From BL until month 24, asthma control test scores improved from 11.6 to 20.3; rescue medication use/week decreased from 5.5 to 1.6 days; mean total number of days of asthma-related medical healthcare use decreased from 7.7 to 0.3 days and missed workdays decreased from 16.8 to 0.3 days. No new safety signals were observed. Add-on omalizumab was effective and well-tolerated in Slovakian patients, complementing the results observed in the overall population of eXpeRience.

New insights in mite immunotherapy - sublingual tablets.

Sublingual tablet immunotherapy has been demonstrated to be effective for allergies induced by exposure to grass, ragweed, specific trees (Japanese Cedar; birch homologous tree mix), and house dust mites (HDM). This review provides both an overview of the evidence-based clinical studies that address the use of the HDM SLIT-tablet for the treatment of HDM-induced allergic rhinitis/conjunctivitis and its appropriate use in carefully selected asthmatic patients and provides the clinician with practical management considerations. Solid evidence-based clinical studies have shown that the HDM SLIT-tablet is both well tolerated in patients with mild-to-moderate asthma and has demonstrated a meaningful improvement in exacerbations, need for rescue medication, quality of life, and asthma control. The HDM SLIT-tablet provides the allergy specialist with a well-tolerated treatment that has established superior safety to subcutaneous injection therapy, which can be administered easily as a sublingual dissolvable tablet, and which provides the opportunity to address one of the more difficult aspects in the management of an inducer of perennial allergic disease - that of persistent airway inflammation and allergic asthma.

Cost-utility of omalizumab for the treatment of uncontrolled moderate-to-severe persistent pediatric allergic asthma in a middle-income country.

Although several randomized clinical trials performed in children 6 years and older with Omalizumab as add-on therapy have reported improvements in diverse clinical outcomes, the evidence regarding its cost effectiveness is not sufficient, especially in less-affluent countries, where the clinical and economic burden of the disease is the greatest. The aim of the present study was to perform a cost-utility analysis of adding omalizumab to standard treatment for treating pediatric patients with uncontrolled severe allergic asthma in Colombia, a middle-income country (MIC). A Markov-type model was developed to estimate costs and health outcomes of a simulated cohort of pediatric patients with persistent asthma treated over a 5-year period. The effectiveness data and transition probabilities were obtained from various sources, including systematic reviews with meta-analysis. Cost data were obtained from official databases provided by the Colombian Ministry of Health. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome was the variable ''quality-adjusted life-years'' (QALYs). For the base-case analysis, the cost-utility analysis showed that compared with the standard treatment strategy, the omalizumab strategy involved higher costs (US$72,142.3 vs. $20,243.4 average cost per patient) and greater gain in QALYs (0.8718 vs. 0.8222 QALYs on average per patient). The incremental cost-utility ratio (ICUR) of omalizumab compared with standard treatment was US$82,748.1 per QALY CONCLUSIONS: This study shows that in Colombia, an MIC, compared with standard treatment, omalizumab is not a cost-effective strategy for treating pediatric patients with uncontrolled severe allergic asthma.

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.

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Cockroach-induced IL9, IL13, and IL31 expression and the development of allergic asthma in urban children

Passive Prophylactic Administration with a Single Dose of Anti-Fel d 1 Monoclonal Antibodies REGN1908-1909 in Cat Allergen-induced Allergic Rhinitis: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

Rationale: Sensitization to Fel d 1 (Felis domesticus allergen 1) contributes to persistent allergic rhinitis and asthma. Existing treatment options for cat allergy, including allergen immunotherapy, are only moderately effective, and allergen immunotherapy has limited use because of safety concerns.Objectives: To explore the relationship among the pharmacokinetic, clinical, and immunological effects of anti–Fel d 1 monoclonal antibodies (REGN1908–1909) in patients after treatment.Methods: Patients received REGN1908–1909 (n = 36) or a placebo (n = 37) in a phase 1b study. Fel d 1–induced basophil and IgE-facilitated allergen binding responses were evaluated at baseline and Days 8, 29, and 85. Cytokine and chemokine concentrations in nasal fluids were measured, and REGN1908–1909 inhibition of allergen–IgE binding in patient serum was evaluated.Measurements and Main Results: Peak serum drug concentrations were concordant with maximal observed clinical response. The anti–Fel d 1 IgE/cat dander IgE ratio in pretreatment serum correlated with Total Nasal Symptom Score improvement. The allergen-neutralizing capacity of REGN1908–1909 was observed in serum and nasal fluid and was detected in an inhibition assay. Type 2 cytokines (IL-4, IL-5, and IL-13) and chemokines (CCL17/TARC, CCL5/RANTES [regulated upon activation, normal T-cell expressed and secreted]) in nasal fluid were inhibited in REGN1908–1909–treated patients compared with placebo (P < 0.05 for all); IL-13 and IL-5 concentrations correlated with Total Nasal Symptom Score improvement. Ex vivo assays demonstrated that REGN1908 and REGN1909 combined were more potent than each alone for inhibiting FcεRI- and FcεRII (CD23)–mediated allergic responses and subsequent T-cell activation.Conclusions: A single, passive-dose administration of Fel d 1–neutralizing IgG antibodies improved nasal symptoms in cat-allergic patients and was underscored by suppression of FcεRI-, FcεRII-, and T-helper cell type 2–mediated allergic responses.Clinical trial registered with www.clinicaltrials.gov (NCT02127801)

Omalizumab as a Therapeutic Option for Nasal Polyposis in Moderate-to-Severe Persistent Allergic Asthma: Evidence From a Prospective Study in a Real-World Setting.

Omalizumab as a Therapeutic Option for Nasal Polyposis in Moderate-to-Severe Persistent Allergic Asthma: Evidence From a Prospective Study in a Real-World Setting.

Efficacy predictors of omalizumab in Chinese patients with moderate-to-severe allergic asthma: Findings from a post-hoc analysis of a randomised phase III study

BackgroundOmalizumab has demonstrated efficacy as an add-on therapy in Chinese patients with moderate-to-severe allergic asthma. This post-hoc analysis assessed the potential predictors for the efficacy of omalizumab in these patients. MethodsA post-hoc analysis was performed on a Phase III, randomised, controlled study conducted in Chinese patients with moderate-to-severe persistent allergic asthma (NCT01202903). We evaluated if levels of pre-treatment serum total immunoglobulin-E (IgE) and blood eosinophil (EOS), asthma severity, allergen profile, history of perennial allergic rhinitis (PAR), and free IgE level during omalizumab treatment were predictive of omalizumab's efficacy. ResultsThis analysis included 608 patients (omalizumab, N = 306; placebo, N = 302). Improvements in forced expiratory volume in 1 s (FEV1), standardized Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE) scores with omalizumab treatment compared with placebo were observed in patients with baseline IgE levels ≥76 IU/mL (irrespective of the EOS count). Relatively greater improvements with omalizumab treatment was also noted in patients with both moderate or severe allergic asthma (regardless of asthma severity), and patients sensitised to >3 allergens and with a history of PAR. All patients who were treated with omalizumab achieved free IgE levels below 50 ng/mL by Week 1. Similar clinical outcomes were observed in the subset of patients who achieved free IgE levels of <25 and ≥ 25 ng/mL. ConclusionsIn Chinese patients with moderate-to-severe allergic asthma, baseline IgE and allergen profile (number/PAR history) are potential predictors of treatment response to omalizumab. Trial registrationNCT01202903 (www.clinicaltrials.gov).

The disease burden in patients with respiratory allergies induced by house dust mites: a year-long observational survey in three European countries

BackgroundHouse dust mite (HDM) allergens constitute the most frequent cause of persistent allergic rhinitis and asthma. The symptoms vary throughout the year but typically peak in spring, autumn and (to a lesser extent) mid-winter.MethodsWe performed a 13-month, observational, multicentre survey of adult patients with a self-reported history of moderate-to-severe, poorly controlled, physician-diagnosed HDM respiratory allergy in three European countries (France, Italy and Spain). After screening and inclusion, 28 detailed, fortnightly telephone interviews were used to gather extensive data on the participants’ symptom prevalence and intensity, medical consultations, disease burden and medication use from late May 2012 to early July 2013. This report focuses on the disease burden.ResultsOf the 22,995 screened participants, 313 met the inclusion criteria and completed the post-inclusion questionnaire (n = 114 in Italy, 92 in France and 107 in Spain). The median time since the first symptoms of HDM allergy was ≥ 13 years in each country. A relevant minority of the participants suffered from symptoms of HDM allergy every day or almost every day of the year (14% in Italy, 46% in France and 37% in Spain). According to the fortnightly telephone interviews, the most frequently impacted disease burden variables were sleep, daytime tiredness and irritability, with the highest values in spring 2012, autumn 2012 and spring 2013 (mirroring symptom intensities). Professional activities were more affected than social activities. The burden data were heterogeneous: around a quarter of participants were strongly or very strongly affected but most of the remaining participants were only rarely bothered or not bothered.ConclusionsIn a 13-month, fortnightly survey of patients in France, Italy and Spain with a self-reported history of moderate-to-severe, poorly controlled, HDM-induced allergic rhinitis and asthma, we found that a relevant minority of participants regularly reported a severe or very severe impact of their allergy on tiredness, sleep and professional activities (including time off work). The disease burden peaked in autumn and late spring.

Effect of pulmonary rehabilitation in an allergen safe outdoor environment on children and adolescents with mild to moderate persistent allergic asthma

Background Environmental interactions are very complex in childhood asthma, and we hypothesized that even a short-term exposure to an allergy safe outdoor environment (AllSOE) combined with pulmonary rehabilitation program (PRP) could exert significant beneficial effects. Our aim was to test the effects of 2-week PRP provided in an AllSOE in children with mild to moderate asthma. Methods 110 children (aged 7.5–17 years, 46% girls), with partially or totally controlled asthma, attended the PRP at the Island of Lošinj (Croatia) supervised by a multidisciplinary team (pediatric pulmonologist, sports medicine specialist, physiotherapist and kinesiologist). Each child had an adjusted intensity of physical activity with at least 2 h of exercise per day. Body height and weight, spirometry, fraction of exhaled nitric oxide (FeNO), running distance during free running test (FRT) and the decline in lung function after FRT (exercise-induced bronchoconstriction- EIB) were measured at baseline and after PRP. Results A significant improvement in running distance (from 903 ± 272 m to 968 ± 289 m; p < 0.001), a decrease of FeNO (from 37 ± 32 ppb to 25 ± 17 ppb; p < 0.001) were determined after PRP. There were no significant changes in lung function and EIB, except EIB in the fourth quartile (significant EIB at baseline) where EIB significantly decreased (p < 0.001) after PRP. Conclusion Two weeks of PRP in an AllSOE significantly improved exercise capacity and reduced airway inflammation and airway hyperreactivity showing that even a short-term PRP within a proper environment could be effective and affordable management strategy for children and adolescents with mild to moderate 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.

Biologic Therapeutics and Their Role in Allergic Disease of the Unified Airway

Recent advances have been made in the use of biologic therapies for chronic inflammatory diseases of the unified airway. The purpose of this review is to summarize the current state of knowledge for biologic therapies in chronic airway disease, including indications for use, mechanisms of action, and future needs for research. There are currently four classes of FDA-approved biologic therapies for treatment of inflammatory airway diseases: Dupilumab (anti-IL-4Rα) is approved for both moderate to severe allergic asthma and chronic rhinosinusitis with nasal polyps, including aspirin-exacerbated respiratory disease. Omalizumab (anti-IgE) is approved for persistent allergic asthma and mepolizumab, reslizumab (both anti-IL-5), and benralizumab (anti-IL-5Rα) are approved for asthma with eosinophilic endotype. Mepolizumab is also approved for eosinophilic granulomatosis with polyangiitis which affects both upper and lower airways. Biologic therapies have offered new treatment options for patients suffering with the most severe forms of allergic airway diseases. The implementation and selection of biologic agents is currently a clinical decision with consideration of disease endotype, co-morbid diseases, and shared decision-making with the patient. Future studies will help determine the comparative performance of these agents, more detailed algorithms for use, long-term outcomes, and safety profiles.

Cost-effectiveness of omalizumab in real world uncontrolled allergic asthma patients

ObjectiveTo estimate the cost-effectiveness of omalizumab compared with standard of care in the treatment and control of severe persistent asthma, using the outcomes from the Portuguese subpopulation of the eXpeRience registry. MethodsThis was a pragmatic cost-effectiveness analysis based on real world data from the eXpeRience registry which recruited 62 patients with uncontrolled persistent allergic asthma from 20 participating centers in Portugal. Response to omalizumab treatment was measured prospectively up to 24 months by the physician’s Global Evaluation of Treatment Effectiveness (GETE). Retrospective data on patients’ clinical symptoms, asthma control, lung function, exacerbations, and healthcare utilization were available for up to 12 months before omalizumab initiation and served as the standard of care comparator. The number of exacerbations (severe and non-severe), the number of clinical episodes, the number of days absent from work and/or school, and GETE response to therapy were considered as effectiveness outcomes. Following a societal perspective, as cost indicators, both direct and indirect costs were considered. Direct costs relate to the cost of omalizumab, standard of care and clinical episodes (emergency room visits, hospitalizations, and unscheduled doctor visits). Indirect costs relate to the societal cost of work absenteeism. Unit costs for clinical episodes and drugs were taken from official sources within the Portuguese Health Authority. A univariate sensitivity analysis was performed. ResultsA rate of 1.5 exacerbations per patient-year was estimated following omalizumab treatment compared with 8.2 exacerbations per patient-year prior to omalizumab initiation, implying an 82.1% reduction in the incidence of exacerbations following omalizumab treatment relative to standard of care alone. A 54.1% reduction in GETE score was also observed in favor of omalizumab treatment. The mean cost per person-year was 3023є in the 12 months of standard of care prior to omalizumab and 16,111є in the period of treatment with omalizumab. The incremental cost-effectiveness ratios were 2244є/exacerbation avoided, and 1750є/unit decrease in GETE classification. ConclusionOur results demonstrate that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations, improving overall treatment effectiveness at an acceptable cost from a societal perspective.