Asthma Exacerbation Rate Research Articles

Relationship between meteorological and environmental factors and acute exacerbation for pediatric bronchial asthma: Comparative study before and after COVID-19 in Suzhou.

Climate and environmental change is a well-known factor causing bronchial asthma in children. After the outbreak of coronavirus disease (COVID-19), climate and environmental changes have occurred. The present study investigated the relationship between climate changes (meteorological and environmental factors) and the number of hospitalizations for pediatric bronchial asthma in Suzhou before and after the COVID-19 pandemic. From 2017 to 2021, data on daily inpatients diagnosed with bronchial asthma at Children's Hospital of Soochow University were collected. Suzhou Meteorological and Environmental Protection Bureau provided daily meteorological and environmental data. To assess the relationship between bronchial asthma-related hospitalizations and meteorological and environmental factors, partial correlation and multiple stepwise regression analyses were used. To estimate the effects of meteorological and environmental variables on the development of bronchial asthma in children, the autoregressive integrated moving average (ARIMA) model was used. After the COVID-19 outbreak, both the rate of acute exacerbation of bronchial asthma and the infection rate of pathogenic respiratory syncytial virus decreased, whereas the proportion of school-aged children and the infection rate of human rhinovirus increased. After the pandemic, the incidence of an acute asthma attack was negatively correlated with monthly mean temperature and positively correlated with PM2.5. Stepwise regression analysis showed that monthly mean temperature and O3 were independent covariates (risk factors) for the rate of acute asthma exacerbations. The ARIMA (1, 0, 0) (0, 0, 0) 12 model can be used to predict temperature changes associated with bronchial asthma. Meteorological and environmental factors are related to bronchial asthma development in children. The influence of meteorological and environmental factors on bronchial asthma may be helpful in predicting the incidence and attack rates.

Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin. The drug has been tested previously in the phase 3 NAVIGATOR (NCT03347279) and SOURCE (NCT03406078) studies, and was subsequently approved as a treatment for severe asthma. This extension study recruited from NAVIGATOR and SOURCE and aimed to evaluate the long-term safety and efficacy of tezepelumab in individuals with severe, uncontrolled asthma. DESTINATION was a phase 3, multicentre, randomised, double-blind, placebo-controlled, long-term extension study. The study was done across 182 sites (including hospitals, clinics, medical centres, clinical trial centres, and private practices) in 18 countries. Participants (aged 12-80 years) were required to have good treatment compliance in the parent study. Randomisation was stratified by the parent study and all participants were re-randomised. Those who were previously randomised to receive tezepelumab in either parent study continued treatment of subcutaneous tezepelumab (210 mg every 4 weeks); those who were previously randomised to receive placebo in either parent study were re-randomised 1:1 to receive either subcutaneous tezepelumab (210 mg every 4 weeks) or placebo (every 4 weeks) using a randomisation list prepared by a computerised system. Total treatment duration (including the parent studies) was 104 weeks for all groups. Participants, investigators, and site staff were masked to treatment assignment. The primary endpoints were exposure-adjusted incidence of adverse events and serious adverse events and the secondary endpoint was the annualised asthma exacerbation rate; these were assessed from week 0 of the parent studies to week 104 of DESTINATION in all participants who were randomised and who received at least one dose of tezepelumab or placebo in either of the parent studies. The trial is registered with ClinicalTrials.gov, NCT03706079, and is closed to new participants. Participants were recruited between Jan 7, 2019, and Oct 15, 2020. For individuals who initially received tezepelumab (n=528) in NAVIGATOR, incidence of adverse events over 104 weeks was 49·62 (95% CI 45·16 to 54·39) per 100 patient-years, compared with 62·66 (56·93 to 68·81) for those receiving placebo (n=531; difference -13·04, 95% CI -17·83 to -8·18). For serious adverse events, incidence was 7·85 (6·14 to 9·89) per 100 patient-years for individuals who initially received tezepelumab and 12·45 (9·97 to 15·35) for those who received placebo (difference -4·59, -7·69 to -1·65). In SOURCE, incidence of adverse events was 47·15 (36·06 to 60·56) per 100 patient-years for those who initially received tezepelumab (n=74) and 69·97 (54·54 to 88·40) for those who received placebo (n=76; difference -22·82, -34·77 to -10·01). For serious adverse events, incidence was 13·14 (7·65 to 21·04) per 100 patient-years for those who initially received tezepelumab and 17·99 (10·66 to 28·44) for those who received placebo (difference -4·85, -14·88 to 4·53). Tezepelumab reduced the annualised asthma exacerbation rate over 104 weeks compared with placebo. In participants initially from NAVIGATOR, the annualised asthma exacerbation rate ratio over 104 weeks was 0·42 (95% CI 0·35 to 0·51); in those initially from SOURCE, the ratio over 104 weeks was 0·61 (0·38 to 0·96). Tezepelumab treatment was well tolerated for up to 2 years and resulted in sustained, clinically meaningful reductions in asthma exacerbations in individuals with severe, uncontrolled asthma. These findings are consistent with previous randomised, placebo-controlled studies and show the long-term safety and sustained efficacy of tezepelumab in individuals with severe, uncontrolled asthma. AstraZeneca and Amgen.

Impacts of Wildfire Smoke and Air Pollution on a Pediatric Population with Asthma: A Population-Based Study.

Wildfires are increasing yearly in number and severity as a part of the evolving climate crisis. These fires are a significant source of air pollution, a common driver of flares in cardiorespiratory disease, including asthma, which is the most common chronic disease of childhood. Poorly controlled asthma leads to significant societal costs through morbidity, mortality, lost school and work time and healthcare utilization. This retrospective cohort study set in Calgary, Canada evaluates the relationship between asthma exacerbations during wildfire smoke events and equivalent low-pollution periods in a pediatric asthma population. Air pollution was based on daily average levels of PM2.5. Wildfire smoke events were determined by combining information from provincial databases and local monitors. Exposures were assumed using postal codes in the health record at the time of emergency department visits. Provincial claims data identified 27,501 asthma exacerbations in 57,375 children with asthma between 2010 to 2021. Wildfire smoke days demonstrated an increase in asthma exacerbations over the baseline (incidence rate ratio: 1.13; 95% CI: 1.02-1.24); this was not seen with air pollution in general. Increased rates of asthma exacerbations were also noted yearly in September. Asthma exacerbations were significantly decreased during periods of COVID-19 healthcare precautions.

Role of social determinants of health in differential respiratory exposure and health outcomes among children

BackgroundAttributes defining the Social Determinants of Health (SDoH) are associated with disproportionate exposures to environmental hazards and differential health outcomes among communities. The dynamics between SDoH, disproportionate environmental exposures, and differential health outcomes are often specific to micro-geographic areas.MethodsThis study focused on children less than 20 years of age who lived in Douglas County, Nebraska, during 2016–2019. To assess the role of SDoH in differential exposures, we evaluated the association between SDoH metrics and criteria pollutant concentrations and the association between SDoH and pediatric asthma exacerbations to quantify the role of SDoH in differential pediatric asthma outcomes. The Bayesian Poisson regression model with spatial random effects was used to evaluate associations.ResultsWe identified significant positive associations between the annual mean concentration of criteria pollutants (carbon monoxide, particulate matter2.5, nitrogen dioxide, sulfur dioxide) with race (Non-Hispanic Black and Hispanic/Latino), financial stability, and literacy. Additionally, there were significant positive associations between higher rates of pediatric asthma emergency department visits and neighborhoods with more Non-Hispanic Black children, children without health insurance coverage, and households without access to a vehicle.ConclusionsNon-Hispanic Black and Hispanic/Latino children living in Douglas County, NE experience disproportionately higher exposure to criteria pollutant concentrations. Additionally, higher rates of asthma exacerbations among Non-Hispanic Black children could be due to reduced access to respiratory care that is potentially the result of financial instability and vehicle access. These results could inform city planners and health care providers to mitigate respiratory risks among these higher at-risk populations.

Течение хронического риносинусита с синоназальным полипозом у пациентов с эозинофильной астмой на фоне лечения

Background: chronic rhinosinusitis (CRS) with polyps is associated with eosinophilic inflammation where interleukin-5 (IL-5) is acting as a key mediator. Commonly, CRS co-exists with asthma. Aim: to assess the efficacy of reslizumab for the treatment of CRS with sinonasal polyposis in patients with severe eosinophilic asthma. Patients and Methods: the study included 21 patients. For the management of severe asthma all patients received reslizumab as intravenous infusion at a dose of 3 mg/kg body weight, once every 4 weeks. CRS with sinonasal polyposis was found in 19 patients, pathological changes of the paranasal sinuses revealed by computer tomography (CT) — in all patients, and symptoms of chronic non-allergic rhinitis with eosinophilia syndrome (NARES) were present in 2 patients. The efficacy of therapy was evaluated 6 months after the beginning of treatment. Over-time changes in the following indicators were evaluated: nasal symptoms, endoscopic pattern of the nasal cavity and paranasal sinuses, total polyp score (TPS), CT findings in the paranasal sinuses, rhinocytogram, blood eosinophil cationic protein level, and eosinophilia. The effectiveness of asthma control was assessed by the reduction in asthma exacerbation rate and the requirements for systemic corticosteroids, as well as the spirometry results and the asthma control test. Results: along with a noticeable improvement of asthma control, 20 patients had clinical, endoscopic and radiological signs of the decrease in severity of nasal symptoms. A more significant improvement of asthma control was achieved in patients with CRS and polyps. The medical histories of patients with CRS and polyps demonstrated that at the early stages of the disease they had NARES symptoms. This finding suggests that NARES could be a predictor of eosinophilic non-IgE-mediated asthma and nasal polyps. Conclusion: the use of reslizumab for the treatment patients with eosinophilic asthma and comorbid CRS with polyps and NARES enables not only to improve the control of asthma symptoms but also to achieve the notable regression of nasal symptoms. KEYWORDS: chronic rhinosinusitis with polyps, asthma, iterleukin-5, reslizumab, non-allergic rhinitis with eosinophilia syndrome. FOR CITATION: Boyko N.V., Churyukina E.V., Lodochkina O.E., Ukhanova O.P. The clinical course of chronic rhinosinusitis with sinonasal polyposis in patients with eosinophilic asthma amid the treatment. Russian Medical Inquiry. 2023;7(2):103–109 (in Russ.). DOI: 10.32364/2587-6821-2023-7-2-103-109.

Allergology: what's new in 2022

The study of reactions to SARS-CoV-2 vaccines has marked a large part of the literature in the last two years, using the basophil activation test (BAT) as a potential diagnostic tool for reactions to Covid-19 vaccines. In allergic rhinoconjunctivitis, lirentelimab (a humanised monoclonal antibody against lectin 8), reduces patients' symptoms and atopic comorbidities. In severe asthma, tezepelumab (human monoclonal antibody) reduces the annual asthma exacerbation rate over 52 weeks. In terms of diet, the new EAACI guidelines recommend avoiding cow's milk supplementation in infants during the first three days of life to reduce the risk of cow's milk allergy.

Real-life efficacy and safety of mepolizumab for eosinophilic granulomatosis with polyangiitis

• Mepolizumab (MPZ), an anti-IL5 monoclonal antibody, is a promising treatment for eosinophilic manifestations in eosinophilic granulomatosis with polyangiitis (EGPA). • Little is known on safety and efficacy of MPZ in EGPA in real-life. • This study provides evidence supporting routine use of MPZ use as a safe and effective treatment for refractory eosinophilic manifestations in patients with EGPA. • An apparent rise in minor infections during MPZ treatment warrants further studies. Little is known about the efficacy and safety of the anti-interleukin 5 monoclonal antibody mepolizumab (MPZ) in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in real-life. We thus evaluated disease activity, damage and disease-related complications in 14 patients with EGPA receiving MPZ for refractory disease for a median time of 16 months in comparison with up to five years before MPZ start. Asthma exacerbation rates, the Birmingham Vasculitis Activity Score and corticosteroid dosage decreased during MPZ ( p < 0.001, p < 0.001 and p = 0.001, respectively). Five patients could discontinue prednisone. Infection rates were higher during MPZ ( p < 10 –6 ), but no rises in hospitalizations, asthma exacerbations or damage accrual were observed. Real-life data confirm the effectiveness of MPZ in refractory EGPA with active asthma. Higher infections rates are in line with other studies and might be due to relative overreporting secondary to increased visit frequency, although a pharmacological effect could not be ruled out.

Temperature-controlled Laminar Airflow (TLA) in symptomatic severe asthma – a post hoc analysis of severe exacerbations, quality of life and health economics

PurposeUncontrolled severe asthma constitutes a major economic burden to society. Add-ons to standard inhaled treatments include inexpensive oral corticosteroids and expensive biologics. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA; Airsonett®) could be an effective, safe and cheaper alternative. The potential of TLA in reducing severe asthma exacerbations was addressed in a recent randomised placebo-controlled trial (RCT) in patients with severe asthma (Global Initiative for Asthma (GINA) step 4/5), but the results were inconclusive. We re-analysed the RCT with severe exacerbations stratified by the level of baseline asthma symptoms and Quality of Life.MethodsMore uncontrolled patients, defined by Asthma Control Questionnaire 7 (ACQ7) > 3, EuroQoL 5-Dimension Questionnaire Visual Analogue Scale (EQ5D-VAS) ≤ 65 and Asthma Quality of Life Questionnaire (AQLQ) ≤ 4 were selected for re-analysis. The rates of severe asthma exacerbations, changes in QoL and health-economics were analysed and compared between TLA and placebo.ResultsThe study population included 226 patients (113 TLA / 113 placebo.) The rates of severe asthma exacerbations were reduced by 33, 31 and 25% (p = 0.083, 0.073, 0.180) for TLA compared to placebo, dependent on selected control measures (ACQ7, EQ5D-VAS, AQLQ, respectively). For patients with less control defined by AQLQ≤4, the difference in mean AQLQ0-12M between TLA and placebo was 0.31, 0.33, 0.26 (p = 0.085, 0.034, 0.150), dependent on selected covariate (AQLQ, EQ5D-VAS, ACQ7, respectively). For patients with poor control defined by ACQ7 > 3, the difference in EQ5D-5 L utility scores between TLA and placebo was significant at 9 and 12 months with a cost-effective ICER. The results from the original study did not demonstrate these differences.ConclusionThis post hoc analysis demonstrated an effect of TLA over placebo on severe exacerbations, asthma control and health economics in a subgroup of patients with more symptomatic severe allergic asthma. The results are consistent with the present recommendations for TLA. However, these differences were not demonstrated in the full study. Several explanations for the different outcomes have been outlined, which should be addressed in future studies.FundingNIHR Health Technology Assessment Programme and Portsmouth Hospitals NHS Trust.

Dupilumab Efficacy and Safety as an Add-On Therapy in Uncontrolled Asthma Patients: A Systematic Review

Asthma is a heterogeneous chronic inflammatory condition affecting the lung. Standard treatment, a high-dose inhaled corticosteroid (ICS) and long-acting bronchodilator (LABA), effectively manages asthma in most individuals. However, 5%-10% of individuals with asthma were ineffective with those treatments. Recent RCTs suggested that Dupilumab posed potential as an add-on therapy. This systematic review aims to support the efficacy (the annualized rate of severe asthma exacerbation and increase in FEV1) and the safety of Dupilumab as an add-on therapy in uncontrolled asthma patients. We used "(Asthma) AND (Dupilumab)" as keywords on PubMed and ScienceDirect. We included only RCT design studies comparing the efficacy and safety of Dupilumab with a placebo in uncontrolled asthma patients. The placebo was ICS and LABA or oral glucocorticoids. This paper included five RCTs with 3400 participants, and their quality was assessed using Critical Appraisal Tools Program (CASP) tools. We conducted a meta-analysis to calculate the pooled risk ratio (RR). In addition, we used Mantel-Haenszel with 95% confidence intervals for dichotomous data. Furthermore, we used a random-effects model to count for interstudy heterogeneity. Then, we processed data using Revman 5.4. Dupilumab as an add-on therapy significantly showed a consistent effect in lower the annualized rate of severe asthma exacerbation (RR= 0.46; 95% CI 0.36- 0.58; p=0.007) and increased FEV1 compared to placebo. In addition, the most common adverse effect of using Dupilumab were injection site reaction, upper respiratory tract infections, and eosinophilia. In conclusion, Dupilumab is safe and well-tolerated as moderate-to-severe uncontrolled asthma add-on therapy

Long-term efficacy of dupilumab in asthma with or without chronic rhinosinusitis and nasal polyps

BackgroundCoexisting chronic rhinosinusitis and nasal polyps (CRS-NPs) substantially increases the disease burden of asthma. Dupilumab, a fully human monoclonal antibody, has established efficacy and an acceptable safety profile in asthma and CRS with NP. ObjectiveTo evaluate long-term dupilumab efficacy in TRAVERSE (NCT02134028) patients with uncontrolled, moderate-to-severe (QUEST) or oral corticosteroid (OCS)-dependent (VENTURE) asthma with or without coexisting CRS-NP. MethodsIn TRAVERSE, 317 of 1530 (21%) QUEST and 61 of 187 (48%) VENTURE patients had self-reported CRS-NP; they received subcutaneous 300 mg dupilumab every 2 weeks up to 96 weeks. Patients were categorized by parent study treatment group (placebo/dupilumab, dupilumab/dupilumab). End points included annualized asthma exacerbation rates and mean change from parent study baseline in prebronchodilator forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, Asthma Quality of Life Questionnaire score, and OCS dose. ResultsPatients with coexisting CRS-NP had higher OCS dose and a history of more exacerbations. Concluding TRAVERSE, exacerbation rates decreased from 2.39 to 0.32 and 2.32 to 0.35 in dupilumab/dupilumab and 2.36 to 0.41 and 2.36 to 0.45 in placebo/dupilumab by week 96 from QUEST and VENTURE baselines, respectively. Non-CRS-NP results were similar. Improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire 5 score, and Asthma Quality of Life Questionnaire score during parent studies were maintained in TRAVERSE; placebo/dupilumab patients achieved similar improvements to dupilumab/dupilumab by week 48. By week 96, 71% and 39% of OCS-dependent patients with CRS-NP and 83% and 47% without CRS-NP treated with dupilumab/dupilumab and placebo/dupilumab, respectively, stopped OCS. ConclusionLong-term dupilumab efficacy was maintained in patients with asthma with or without self-reported coexisting CRS-NP, including OCS-sparing effects observed in OCS-dependent severe asthma. Clinical Trial RegistrationClinicalTrials.gov Identifiers: NCT02528214, NCT02414854, and NCT02134028.

EFFECT OF SEX ON RESPONSE TO OMALIZUMAB IN PATIENTS WITH ASTHMA

<h3>Introduction</h3> There are sex-related disparities in asthma. Before puberty, males have increased prevalence and severity of asthma compared with females, and this pattern reverses after the onset of puberty. Omalizumab, an IgE antibody, is an effective treatment for allergic asthma, but sex-specific responses have not been studied in detail. <h3>Methods</h3> Post hoc analysis examined data from randomized, placebo-controlled IA05 trial of omalizumab treatment (52 weeks; 75-375 mg sc every 2-4 weeks; N=627; 6 to <12 years, ie children) and open-label, single-arm PROSPERO study (NCT01922037; 48-weeks; N=801; ≥12 years ie adolescents/adults (n=732 ≥18 years); both included patients with moderate-severe allergic asthma. <h3>Results</h3> In IA05/PROSPERO, baseline characteristics of mean age and IgE levels were similar for female and male participants (females 8.4/47.8 versus males 8.6/46.2 years; IgE levels females 463.2/560.3 versus males 472.8/615.0 IU/mL). Asthma exacerbation rates following omalizumab treatment were similar for females and males. In IA05 (children), asthma exacerbation rates were: females - placebo 0.74 versus omalizumab 0.46, males - placebo 0.55 versus omalizumab 0.43, and the interaction test of effect of sex on omalizumab response was not significant (p=0.4821). In PROSPERO (adolescents/adults), asthma exacerbation rates in females were 0.74 versus males 0.77 (p=0.787). Overall safety reported previously for IA05, Lanier JACI 2009;124;1210-6 and PROSPERO, Casale JACI:IP 2019;7(1):156-64. <h3>Conclusions</h3> Despite differences in asthma between females and males, we found no evidence that the effect of omalizumab in children was dependent on sex, and no evidence that the rate of exacerbations was dependent on sex following omalizumab initiation in adolescents/adults.

LONG-TERM DUPILUMAB REDUCES EXACERBATIONS AND IMPROVES LUNG FUNCTION IN TYPE 2 PATIENTS WITH/WITHOUT ALLERGIC

<h3>Introduction</h3> TRAVERSE (NCT02134028) assessed dupilumab long-term safety and efficacy in patients ≥12 years who previously completed a dupilumab asthma study. Safety was consistent with the known dupilumab safety profile. This analysis of TRAVERSE evaluated dupilumab long-term efficacy in patients who previously participated in QUEST (NCT02414854) and had type 2 asthma (blood eosinophils ≥150cells/µL or fractional exhaled nitric oxide [FeNO] ≥20ppb) with or without an allergic phenotype (serum total IgE ≥30IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35kU/L) at parent study baseline and history of ≥2 exacerbations in the year prior to QUEST. <h3>Methods</h3> In TRAVERSE, patients received dupilumab 300mg q2w for up to 96 weeks (dupilumab/dupilumab and placebo/dupilumab groups). Unadjusted annualized severe asthma exacerbation rate (AER) and change from QUEST baseline FEV₁ were assessed. <h3>Results</h3> In Year 1 of treatment (QUEST), dupilumab vs placebo reduced AER to 0.578/1.490 and 0.470/1.476 in patients with and without an allergic phenotype, respectively. In Year 2 (TRAVERSE Weeks 0–48), AER was further reduced to 0.474/0.591 and 0.320/0.295 in dupilumab/dupilumab- vs placebo/dupilumab-treated patients with and without an allergic phenotype, respectively; in Year 3 (TRAVERSE Weeks 48–96), AER was 0.353/0.203 and 0.214/0.268, respectively. Dupilumab sustained FEV₁ improvements in the dupilumab/dupilumab group and rapidly improved lung function in the placebo/dupilumab group after initiating dupilumab in TRAVERSE (<b>Figure</b>). <h3>Conclusions</h3> Dupilumab sustained reductions in exacerbations and improvements in FEV₁ for up to 3 years in patients with uncontrolled, moderate-to-severe type 2 asthma with a history of ≥2 exacerbations prior to study start, regardless of evidence of allergic asthma.

ASTHMA EXACERBATIONS BEFORE AND AFTER TEZEPELUMAB TREATMENT: A POOLED ANALYSIS OF PATHWAY AND NAVIGATOR STUDIES

<h3>Introduction</h3> Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the PATHWAY and NAVIGATOR studies, tezepelumab reduced asthma exacerbations versus placebo in patients with severe, uncontrolled asthma, irrespective of baseline blood eosinophil count (BEC), allergic status and maintenance oral corticosteroid (mOCS) use. This post hoc pooled analysis assessed the effect of tezepelumab on asthma exacerbations 12 months before and after treatment initiation. <h3>Methods</h3> PATHWAY (NCT02054130) and NAVIGATOR (NCT03347279) were multicenter, randomized, placebo-controlled studies with similar designs. Patients (12–80 years old) who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for up to 52 weeks were included. The mean number and rate of asthma exacerbations (accounting for time-at-risk) were summarized over 12 months before and after treatment initiation, respectively, for the overall pooled population and subgroups of baseline BEC, perennial allergic status and mOCS use. <h3>Results</h3> Overall, 1334 patients were included (tezepelumab, n=665; placebo, n=669). In the 12 months before treatment, the mean number of asthma exacerbations was similar between treatment groups in the overal population and across subgroups, except for those receiving mOCS (<b>Figure</b>). After up to 12 months of treatment, the rate of asthma exacerbations was lower with tezepelumab than the mean number of exacerbations before treatment and lower than the rate in the placebo group, overall and across subgroups (<b>Figure</b>). <h3>Conclusion</h3> Patients experienced fewer exacerbations after initiating tezepelumab treatment compared with the 12 months before treatment and compared with the placebo group. Similar reductions were observed irrespective of BEC, allergic status or mOCS use.

REAL WORLD EFFECTIVENESS OF MEPOLIZUMAB IN PATIENTS WITH ALLERGIC AND NON-ALLERGIC ASTHMA

<h3>Introduction</h3> Eosinophilia provides a common denominator for overlapping allergic and non-allergic asthma phenotypes and offers a basis for the efficacy of mepolizumab. While efficacy and safety of mepolizumab in severe asthma is well-documented, comparative effectiveness data among allergic and non-allergic phenotypes is limited. This study compared the impact of treatment with mepolizumab on patients with allergic versus non-allergic asthma. <h3>Methods</h3> This was a retrospective cohort study using administrative claims data from Optum Research Database. The study population included patients with asthma (>=6 years) initiated on mepolizumab between January 2016–December 2019. The asthma exacerbation rate and OCS use were assessed in both the 12 months before (baseline period) and 12 months following (follow-up period) mepolizumab initiation. Allergic status was ascertained using diagnosis codes, medication use and lab test results. <h3>Results</h3> In total 240 (44.6%) allergic and 298 (55.4%) non-allergic asthma patients met eligibility criteria. The mean (SD) asthma exacerbation rate was substantially reduced from baseline to follow-up for both allergic asthma (3.19[2.49] to 2.10[2.12], p<0.001) and non-allergic asthma patients (2.51[2.17] to 1.70[1.92], p<0.001). Significant reduction was also observed with regards to mean (SD) count of OCS claims from baseline to follow-up for patients with allergic (5.19[4.47] to 3.46[4.50], p<0.001) and non-allergic asthma (5.46[4.12] to 3.20[3.69], p<0.001). No significant differences were observed between cohorts in the decreases in asthma exacerbations or counts of OCS claims from baseline to follow-up. <h3>Conclusion</h3> This study supports the real-world effectiveness of mepolizumab for the treatment of severe asthma with allergic and non-allergic phenotypes.

Tezepelumab for Patients with Severe Uncontrolled Asthma: A Systematic Review and Meta-Analysis.

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. It was approved by the United States Federal Drug Administration (US FDA) as an add-on maintenance treatment for patients with severe uncontrolled asthma in December 2021. We conducted a systematic review and meta-analysis to investigate the safety and efficacy of tezepelumab on forced expiratory volume (FEV1) (L), the rate of asthma exacerbations, health-related quality of life, fractional exhaled nitric oxide (FeNO) (ppb), and blood eosinophil count (cells/mL) in patients with severe, uncontrolled asthma. Mean changes for efficacy and proportions (safety) with their corresponding 95% confidence intervals (CIs) were used to provide pooled estimates. A total of six randomized controlled trials comprising 2667 patients were included, of whom 1610 were treated with tezepelumab and 1057 received placebo. The pooled analysis showed that tezepelumab treatment resulted in an improvement in FEV1 of 0.15 L (95% CI: 0.12 to 0.17), a reduction in the asthma exacerbation rate per year of 0.60 (95% CI: 0.51 to 0.70), and a reduction in FeNO of -12.41 ppb (95% CI: -14.28 to -10.53) when compared to placebo. Improvements in FEV1 and FeNO levels were maintained at 24 and 52 weeks. As for safety, patients did not experience a higher incidence of adverse drug reactions with tezepelumab (0.79 (95% CI: 0.55 to 1.12)) as compared to placebo. As for quality of life, different doses of the tezepelumab intervention group depicted non-significant improvement in the QoL, from 0.15 (95% CI: -0.09 to 0.38) for 70 mg, 0.18 (95% CI: -0.10 to 0.46) for 210 mg, 0.08 (95% CI: -0.16 to 0.32) for 280 mg as compared to the placebo. Tezepelumab significantly reduced exacerbation rates and improved FEV1 with an acceptable safety profile.

REAL-WORLD BENRALIZUMAB EFFECTIVENESS AMONG ASTHMA PATIENTS WITH COMORBID NASAL POLYPS: RESULTS FROM THE ZEPHYR2 STUDY

<h3>Introduction</h3> Benralizumab demonstrated significant reductions in asthma exacerbations among asthma patients with comorbid nasal polyps (NP). This study characterized the real-world effectiveness of benralizumab pre- vs. post-initiation in a population stratified by prior NP surgery. <h3>Methods</h3> In this pre-post study, asthma patients with comorbid NP were identified from a large US insurance claims database (11/2016–6/2020). Patients were aged ≥12 years, with ≥2 records of benralizumab, ≥2 exacerbations pre-benralizumab use (index date), and an NP diagnosis in the 12-months pre-index. Patients were stratified by NP surgery in the 12-months pre-index. Asthma exacerbation rates and NP-related outpatient and oral corticosteroid (OCS) use were described and compared between the 12-month pre-index and post-index periods. <h3>Results</h3> Among the 241 patients identified, 66 had pre-index NP surgery and 175 did not. The surgery cohort had on average 2.5 pre-index NP surgeries vs. 0.3 post-index. The non-surgery cohort had 0 pre-index vs. 0.4 surgeries post-index. The overall NP cohort experienced a 58% reduction in exacerbation rates, with a 57% reduction seen in the surgery cohort and a 59% reduction in the non-surgery cohort (all p<0.001, see Figure). Percentages of patients with NP-related outpatient visits (surgery: 100% pre-index vs. 61% post-index; non-surgery: 96% vs. 62%; both p<0.001) and OCS use (surgery: 79% vs. 36%; non-surgery: 78% vs. 37%; both p<0.001) decreased in both cohorts. <h3>Conclusion</h3> In the pre-post analysis, patients with asthma and comorbid NP, irrespective of NP surgery profile, experienced significant reductions in asthma exacerbations, NP-related outpatient visits and OCS use following benralizumab.

REAL-WORLD EFFECTIVENESS OF DUPILUMAB IN ASTHMA: FINDINGS FROM THE US ADVANTAGE STUDY

<h3>Introduction</h3> Real-world evidence on patients with moderate-to-severe asthma treated with dupilumab is limited. Patients included in clinical trials may differ from the ones seen on a clinical office setting. The objective of our study was to characterize real-world effectiveness of dupilumab in US, as an add-on treatment in patients with moderate to severe asthma. <h3>Methods</h3> We retrospectively included patients (≥12 years of age) diagnosed with asthma, initiating dupilumab (index) between November 2018 to September 2020, with 12 months pre- and post-index information. The study employed a pre-post self-control design (TriNetX Dataworks, USA). Asthma exacerbation rates before vs. after dupilumab initiation were analyzed using Generalized Estimating Equations models with Poisson probabilistic link to estimate incidence rate ratios (IRRs). Sensitivity analyses on asthma exacerbations adjusted for COVID-19 confounding effects were performed using natural cubic splines to allow for time-varying effect estimates during pre- and post-pandemic time periods. <h3>Results</h3> A total of 2400 patients initiating dupilumab met all study criteria and 75.3% were biologic naïve. Dupilumab reduced risk of asthma exacerbations by 38% (IRR: 0.62 [95% confidence interval: 0.58-0.65], P=<.0001). Significant reductions in asthma exacerbations were observed in patients with at least 1 or 2, pre-index, asthma exacerbations, by eosinophil count categories, and when adjusted for impact of COVID-19 (Table-1) <h3>Conclusion</h3> The US ADVANTAGE study demonstrated real-world effectiveness of dupilumab in reducing asthma exacerbation among patients 12 years and older in US clinical practice. These findings are generally consistent with data from previous pivotal clinical trials with dupilumab.

LONG-TERM SAFETY AND EFFICACY OF DUPILUMAB IN CHILDREN WITH ASTHMA: LIBERTY ASTHMA EXCURSION

<h3>Introduction</h3> Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13. Efficacy and safety of dupilumab in children with asthma have been demonstrated up to 52 weeks in VOYAGE (NCT02948959). <h3>Methods</h3> 365 pediatric participants who completed VOYAGE entered EXCURSION (NCT03560466), a 52-week open-label study of dupilumab 100/200mg (body-weight based) every 2 weeks; a patient subgroup received 300mg every 4 weeks. Treatment-emergent adverse events, blood eosinophil count, total serum IgE, annualized rate of severe asthma exacerbations (AER), and change from VOYAGE baseline in percent predicted forced expiratory volume in 1 second (ppFEV₁) were assessed. <h3>Results</h3> Dupilumab was well tolerated, and the safety profile was consistent with the parent study (<b>Table</b>). Blood eosinophil count decreased from baseline in VOYAGE with median changes (Q1:Q3) of -140 (-410:10) cells/µL at EXCURSION Week 52 for dupilumab/dupilumab (n=191) and -30 (-260:70) cells/µL for placebo/dupilumab (n=105). Total IgE declined substantially throughout EXCURSION with median percent change from VOYAGE baseline to EXCURSION Week 52 of -89.9% for dupilumab/dupilumab (-339.0 IU/mL; n=219) and -80.0% for placebo/dupilumab (-278.0 IU/mL; n=114). Median total IgE at Week 52 was 40.5 and 53.5 IU/mL for dupilumab/dupilumab and placebo/dupilumab, respectively. The low unadjusted AER and improved ppFEV₁ observed in VOYAGE were sustained in patients with type 2 inflammatory phenotype (<b>Table</b>). <h3>Conclusion</h3> Long-term use of dupilumab was well tolerated, with a decline in type 2 biomarkers including blood eosinophils and total serum IgE. Efficacy observed in VOYAGE in patients with type 2 asthma was sustained in EXCURSION over an additional 52 weeks.

EFFICACY OF TEZEPELUMAB IN PATIENTS WITH SEVERE, UNCONTROLLED ASTHMA AND HIGH BASELINE BLOOD EOSINOPHIL COUNTS

<h3>Introduction</h3> The efficacy of biologics for severe asthma is greater in patients with higher blood eosinophil counts (BECs) than those with lower BECs. Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced the annualized asthma exacerbation rate (AAER) in patients with severe, uncontrolled asthma, irrespective of baseline BECs. This exploratory analysis assessed the efficacy of tezepelumab in patients with high baseline BECs (≥ 500 cells/μL) in NAVIGATOR. <h3>Methods</h3> NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. At week 52, AAER and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV₁) were assessed by baseline BEC (≥ 500, ≥ 750 and ≥ 1000 cells/μL). <h3>Results</h3> Of 1059 patients, 209 had BECs ≥ 500 cells/μL, 76 had BECs ≥ 750 cells/μL and 33 had BECs ≥ 1000 cells/μL at baseline. Among placebo recipients, AAERs increased with increasing BEC. Tezepelumab reduced the AAER versus placebo by 74–77% across these BEC subgroups (<b>Figure</b>). Tezepelumab improved pre-BD FEV₁: least squares mean differences versus placebo were 0.26 L (95% confidence interval [CI]: 0.15–0.37), 0.21 L (95% CI: 0.02–0.40) and 0.41 L (95% CI: 0.13–0.69) in patients with baseline BECs ≥ 500, ≥ 750 and ≥ 1000 cells/μL, respectively. <h3>Conclusion</h3> Tezepelumab substantially reduced exacerbations and improved lung function versus placebo in patients with severe, uncontrolled asthma across all subgroups with high baseline BECs.

EFFICACY OF BIOLOGICS IN PATIENTS WITH SEVERE ALLERGIC ASTHMA, OVERALL AND BY BLOOD EOSINOPHIL COUNT

<h3>Introduction</h3> Patients with uncontrolled, severe allergic asthma may be prescribed biologic therapies to reduce exacerbations and improve disease control. Randomized controlled trials (RCTs) of these therapies have differed in design, with varying results overall and by baseline blood eosinophil count (BEC). Here we describe annualized asthma exacerbation rate (AAER) reductions from RCTs in patients with severe allergic asthma overall and by baseline BEC category. <h3>Methods</h3> A literature search was performed to identify published phase 3 RCT data of FDA-approved biologics in patients with severe, uncontrolled asthma with confirmed allergy to perennial aeroallergens, where AAER reduction versus placebo was measured in the overall population and/or in those with a high or low BEC at baseline or screening. <h3>Results</h3> The serum total immunoglobulin E levels varied between biologic RCT analyses. In the overall allergic population, data were available for tezepelumab, dupilumab and omalizumab only; the greatest AAER reduction was observed with tezepelumab. In patients with allergy and BECs of at least 260 cells/μL or at least 300 cells/μL or higher, AAER reductions were observed with all biologics; the smallest AAER reduction was observed with omalizumab. In patients with allergy and BEC less than 300 cells/μL (regardless of historical BEC), an AAER reduction was observed with tezepelumab but not with mepolizumab, benralizumab or omalizumab. (<b>Figure</b>). <h3>Conclusion</h3> Among patients with severe allergic asthma, tezepelumab was the only biologic to demonstrate reductions consistently in AAER across all subgroups. The efficacy of biologics varies considerably overall and by BEC. These differences can inform provider treatment decisions.