scholarly journals Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mark C. Liu ◽  
Bradley Chipps ◽  
Xavier Munoz ◽  
Gilles Devouassoux ◽  
Miguel Bergna ◽  
...  
Keyword(s):  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
High Dose ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Post Hoc Analysis ◽  
Severe Eosinophilic Asthma ◽  
Baseline Characteristics ◽  
Post Hoc

Abstract Background The OSMO study assessed the efficacy of switching to mepolizumab in patients with severe eosinophilic asthma that was uncontrolled whilst receiving omalizumab. The objective of this analysis was to assess the proportion of patients achieving pre-defined improvements in up to four efficacy outcomes and the relationship between patient baseline characteristics and treatment response. Methods This was a post hoc analysis of OSMO study data (GSK ID:204471; ClinicalTrials.gov No. NCT02654145). Patients with severe eosinophilic asthma uncontrolled by high-dose inhaled corticosteroids, other controller(s) and omalizumab subcutaneously (≥ 4 months) were switched to mepolizumab 100 mg administered subcutaneously. Endpoints included the proportion of responders—i.e. patients achieving a pre-defined clinical improvement in ≥ 1 of the following outcomes: (1) Asthma Control Questionnaire (ACQ)-5 score (≥ 0.5-points), (2) St George’s Respiratory Questionnaire (SGRQ) total score (≥ 4-points), (3) pre-bronchodilator forced expiratory volume in 1s (FEV1; ≥ 100 mL), all at Week 32, and (4) annualised rate of clinically significant exacerbations (≥ 50% reduction). Results Of the 145 patients included, 94%, 83%, 63% and 31% were responders for ≥ 1, ≥ 2, ≥ 3 and 4 outcomes, respectively; 75% and 78% were ACQ-5 and SGRQ score responders, and 50% and 69% were FEV1 and exacerbation responders. Subgroup analyses demonstrated improvements irrespective of baseline blood eosinophil count, prior omalizumab treatment regimen/duration, comorbidities, prior exacerbation history, maintenance oral corticosteroid use, ACQ-5 and SGRQ scores, and body weight/body mass index. Conclusions After switching to mepolizumab, almost all patients with uncontrolled severe eosinophilic asthma on omalizumab achieved a beneficial response in ≥ 1 clinical outcome. Improvements were observed regardless of baseline characteristics. Trial registration This manuscript is a post hoc analysis of data from the OSMO study. ClinicalTrials.gov, NCT02654145. Registered January 13, 2016.

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals Efficacy of one time per day, single-inhaler indacaterol/glycopyrronium/mometasone in patients with inadequately controlled asthma: post hoc analysis of IRIDIUM study in Asian population

2021 ◽  
Vol 8 (1) ◽  
pp. e000856 ◽  
Author(s):  
Hironori Sagara ◽  
Nathalie Barbier ◽  
Tsuyoshi Ishii ◽  
Hajime Yoshisue ◽  
Ivan Nikolaev ◽  
...  
Keyword(s):  
Lung Function ◽  
Asthma Control ◽  
Inhaled Corticosteroids ◽  
High Dose ◽  
Asthma Control Questionnaire ◽  
Post Hoc Analysis ◽  
Asian Patients ◽  
Asthma Exacerbations ◽  
Post Hoc ◽  
Medium Dose

Background and objectiveThe 52-week IRIDIUM study demonstrated the efficacy of indacaterol acetate/glycopyrronium bromide/mometasone furoate (IND/GLY/MF) versus IND/MF and salmeterol xinafoate/fluticasone propionate (SAL/FLU) in patients with symptomatic asthma, despite long-acting β2-agonist/inhaled corticosteroids (LABA/ICS) medium-dose or high-dose, predicted forced expiratory volume in 1 s (FEV1) <80% and at least one exacerbation in the previous year. Here, we present data from a post hoc analysis of the IRIDIUM study in the Asian subpopulation.MethodsThis post hoc analysis evaluated improvements in lung function, asthma control and reduction in asthma exacerbations with IND/GLY/MF medium- (150/50/80 µg) and high-dose (150/50/160 µg) versus IND/MF medium- (150/160 µg) and high-dose (150/320 µg), all one time per day and SAL/FLU high-dose (50/500 µg) two times per day, in Asian patients from the IRIDIUM study.ResultsIn total, 258 patients (IND/GLY/MF medium-dose, 52; IND/GLY/MF high-dose, 52; IND/MF medium-dose, 51; IND/MF high-dose, 51; SAL/FLU high-dose, 52) were included. IND/GLY/MF medium- and high-dose showed greater improvement in trough FEV1 at week 26 versus respective doses of IND/MF (Δ, 100 mL and 101 mL; both p<0.05, respectively), and SAL/FLU high-dose (Δ, 125 mL; p=0.0189, and 136 mL; p=0.0118, respectively), which were maintained over 52 weeks. Both doses of IND/GLY/MF showed greater improvement in morning and evening peak expiratory flow versus respective doses of IND/MF and SAL/FLU high-dose at week 52. The changes in Asthma Control Questionnaire-7 scores from baseline were comparable in all treatment groups. IND/GLY/MF medium- and high-dose showed greater reductions in severe (34%, 69%), moderate or severe (18%, 54%) and all exacerbations (21%, 34%) compared with SAL/FLU high-dose over 52 weeks.ConclusionOne time per day, single-inhaler IND/GLY/MF improved lung function, reduced asthma exacerbations and provided comparable asthma control versus IND/MF and SAL/FLU in Asian patients with inadequately controlled asthma despite LABA/ICS. The results of this analysis were consistent with the overall population in the IRIDIUM study.

scholarly journals Mepolizumab effectiveness and identification of super-responders in severe asthma

2020 ◽  
Vol 55 (5) ◽  
pp. 1902420 ◽  
Author(s):  
Erin S. Harvey ◽  
David Langton ◽  
Constance Katelaris ◽  
Sean Stevens ◽  
Claude S. Farah ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Real World ◽  
Rate Ratio ◽  
Disease Burden ◽  
Symptom Control ◽  
Blood Eosinophil ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Peripheral Blood Eosinophil ◽  
Severe Eosinophilic Asthma

Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population.The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia.Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL−1. Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%.Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41); p<0.001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63); p<0.001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline.Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.

scholarly journals Eosinophils Target Therapy for Severe Asthma: Critical Points

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Brussino ◽  
E. Heffler ◽  
C. Bucca ◽  
S. Nicola ◽  
G. Rolla
Keyword(s):  
Severe Asthma ◽  
Eosinophil Count ◽  
Inhaled Corticosteroids ◽  
Response To Treatment ◽  
High Dose ◽  
Blood Eosinophil ◽  
Moderate Increase ◽  
Eosinophilic Asthma ◽  
Peripheral Blood Eosinophil ◽  
Blood Eosinophil Count

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.

scholarly journals The effectiveness of benralizumab in the treatment of the eosinophilic phenotype of severe asthma in real clinical practice

2021 ◽  
Vol 31 (5) ◽  
pp. 628-634
Author(s):  
Olga N. Titova ◽  
Natalia A. Kuzubova ◽  
Daria B. Sklyarova ◽  
Maria A. Petrova
Keyword(s):  
Clinical Practice ◽  
Asthma Control ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Current Therapy ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
Night And Day ◽  
Real Clinical Practice

To evaluate the effectiveness of benralizumab in patients with the eosinophilic phenotype of severe asthma in real clinical practice after a year of therapy.Methods. During Benralizumab therapy, 13 patients with severe eosinophilic asthma (average age – 55.44 ± 7.18 years old) were examined twice: before the treatment and after 1 year of benralizumab therapy. The assessment included collection of complaints, medical history, current therapy, Asthma Control Questionnaire (ACQ-5) test, absolute blood count of eosinophils, spirometry.Results. All patients initially had pronounced eosinophilia of 577.5 ± 356.4 cells/μl. After 1 year of using benralizumab, the eosinophil count decreased by 96.15%. During therapy, the ACQ-5 index decreased from 1.63 ± 0.62 to 0.73 ± 0.41 in the study patients, which corresponded to the achievement of asthma control. The forced expiratory volume in 1 second (FEV1) increased by 23 %. The number of exacerbations decreased by 58.09%. 12 (92.31%) patients were on oral corticosteroids (OCS) (10 ± 2.17 mg of prednisolone daily) before benralizumab therapy. All subjects noted a decrease in night and day symptoms over time and were able to reduce the use of OCS. 5 (38.46%) patients achieved complete elimination of daily OCS use, 7 (53.84%) patients were able to reduce their daily OCS dose.Conclusion. Benralizumab therapy as an add-on maintenance treatment in patients with eosinophilic phenotype of severe asthma contributes to a significant decrease in peripheral blood eosinophils, which mediates an improvement in asthma control, an increase in FEV1, a reduction in the number of exacerbations, and a decrease in the need for the OCS usage. Careful monitoring of long-term adverse events is necessary during treatment with benralizumab.

scholarly journals Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Peter G. Gibson ◽  
Charlene M. Prazma ◽  
Geoffrey L. Chupp ◽  
Eric S. Bradford ◽  
Mark Forshag ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Asthma Control ◽  
Severe Asthma ◽  
Forced Expiratory Volume ◽  
Comorbid Conditions ◽  
Eosinophilic Asthma ◽  
Asthma Control Questionnaire ◽  
Severe Eosinophilic Asthma ◽  
St George's Respiratory Questionnaire ◽  
Clinically Significant

Abstract Background Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities. Methods This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline. Results Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup. Conclusions Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity. Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

scholarly journals Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mona Bafadhel ◽  
Dave Singh ◽  
Christine Jenkins ◽  
Stefan Peterson ◽  
Thomas Bengtsson ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Inhaled Corticosteroids ◽  
Forced Expiratory Volume ◽  
Cox Proportional Hazards ◽  
Chronic Obstructive ◽  
Blood Eosinophil ◽  
Protective Effects ◽  
Increased Risk ◽  
Post Hoc ◽  
Reduced Risk

Abstract Background Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. Methods This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV1] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. Results The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69–84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. Conclusions Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.

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