Anti-IL5 therapy could prevent lung function decline in severe eosinophilic asthma: data from the belgian severe asthma registry

Background: Severe eosinophilic asthma decreases lung function and causes worsen symptoms, often forcing recurrent maintenance corticosteroid use. The aim of our real-life study was to evaluate the effectiveness of an add-on treatment with benralizumab in patients with severe eosinophilic asthma, paying particular attention to the impact on their quality of life (QoL).Materials and methods: In this prospective study, 10 outpatients with severe eosinophilic asthma were added-on with benralizumab and followed-up in our severe asthma clinic after 12 and 24 weeks. At each patient visit, pre-bronchodilator FEV1 and inflammatory markers were recorded. Variations in asthma symptoms control and QoL perception was assessed by validated questionnaires.Results: All the subjects experienced a marked reduction of nocturnal and diurnal symptoms over time and were able to stop using OCS, as documented by the improvement in Asthma control test (ACT) and Asthma Control Questionnaire score. Similarly, we recorded a statistically significant increase in patient’s QoL perception in EQ-VAS, EQ-5D-3L and Asthma Quality of Life Questionnaire (AQLQ) assessment (p < 0.05). Simultaneously we recorded a significant reduction in eosinophilic inflammation, an improvement in pre-bronchodilator FEV1. These results appear to be in line with those already obtained in the previous randomized controlled trials (RCTs).Conclusion: Our 24-weeks real life experience supports the effectiveness of an add-on treatment with benralizumab in reducing eosinophilic inflammation and OCS-use, increasing lung function and improving control of nocturnal and diurnal symptoms, as well as restoring severe asthma patients to a better QoL.

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Clusters of Severe Eosinophilic Asthma in a Korean Asthma Cohort

Respiration ◽

10.1159/000520492 ◽

2021 ◽

pp. 1-11

Author(s):

Ji-Hyang Lee ◽

Jin An ◽

Ha-Kyeong Won ◽

Bomi Seo ◽

Jung-Hyun Kim ◽

...

Keyword(s):

Cluster Analysis ◽

Lung Function ◽

Severe Asthma ◽

Treatment Options ◽

Clinical Importance ◽

Forced Expiratory Volume ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Patient Subgroups

Background: Targeted therapies have broadened the available treatment options for patients with severe eosinophilic asthma (SEA). However, differences in the magnitude of treatment responses among patients indicate the presence of various underlying pathophysiological processes and patient subgroups. Objectives: We aimed to describe the characteristics of SEA and identify its patient subgroups. Methods: Clinical data from the Cohort for Reality and Evolution of Adult Asthma in Korea were analyzed. Cluster analysis was performed among those with SEA using 5 variables, namely, prebronchodilator forced expiratory volume in 1 s, body mass index, age at symptom onset, smoking amount, and blood eosinophil counts. Results: Patients with SEA showed prevalent sensitization to aeroallergens, decreased lung function, and poor asthma control status. Cluster analysis revealed 3 distinctive subgroups among patients with SEA. Cluster 1 (n = 177) consisted of patients reporting the lowest blood eosinophils (median, 346.8 cells/μL) and modest severe asthma with preserved lung function during the 12-month treatment period. Cluster 2 (n = 42) predominantly included smoking males with severe persistent airway obstruction and moderate eosinophilia (median, 451.8 cells/μL). Lastly, cluster 3 (n = 95) included patients with the most severe asthma, the highest eosinophil levels (median, 817.5 cells/μL), and good treatment response in terms of improved lung function and control status. Conclusions: Three subgroups were identified in SEA through the cluster analysis. The distinctive features of each cluster may help physicians predict patients who will respond to biologics with greater magnitude of clinical improvement. Further research regarding the underlying pathophysiology and clinical importance of each subgroup is warranted.

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Efficacy and Safety of Mepolizumab in Uncontrolled Patients with Severe Eosinophilic Asthma Following a Switch from Omalizumab (OSMO Study): Asthma Control, Quality of Life and Lung Function Outcomes

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2017.12.964 ◽

2018 ◽

Vol 141 (2) ◽

pp. AB408 ◽

Cited By ~ 4

Author(s):

Frank C. Albers ◽

Mark C. Liu ◽

Bradley E. Chipps ◽

Kenneth R. Chapman ◽

Xavier Muñoz ◽

...

Keyword(s):

Quality Of Life ◽

Lung Function ◽

Asthma Control ◽

Efficacy And Safety ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Control Quality

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Severe eosinophilic bronchial asthma: new therapeutic options

Medical Council ◽

10.21518/2079-701x-2018-15-44-52 ◽

2018 ◽

pp. 44-52 ◽

Cited By ~ 2

Author(s):

N. M. Nenasheva

Keyword(s):

Monoclonal Antibodies ◽

Severe Asthma ◽

Bronchial Asthma ◽

Biological Agents ◽

Therapeutic Options ◽

Clinical Use ◽

Eosinophilic Asthma ◽

Interleukin 5 ◽

Severe Eosinophilic Asthma

Eosinophilic asthma is a common phenotype of severe asthma, occurring in at least half of patients. In recent years, there have been significant changes in the approaches to the treatment of severe bronchial asthma and, above all, eosinophilic asthma. The article discusses the role of eosinophils in the pathogenesis of severe asthma, the detection of the phenotype of severe eosinophilic asthma, and modern approaches to targeting severe asthma with an eosinophilic phenotype using biological agents. A special emphasis is placed on preparations of monoclonal antibodies to interleukin-5, in particular, mepolizumab, recently approved for clinical use in our country.

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Precision medicine applications for severe asthma

LymphoSign Journal ◽

10.14785/lymphosign-2019-0017 ◽

2019 ◽

Vol 6 (4) ◽

pp. 117-135

Author(s):

Orit Gourgy Hacohen ◽

Shai Cohen

Keyword(s):

Precision Medicine ◽

Severe Asthma ◽

Oral Corticosteroid ◽

Treatment Options ◽

Current Evidence ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Beneficial Effects ◽

New Treatment

Asthma is a heterogeneous condition in which multiple pathological pathways manifest with similar symptoms. Severe asthma (SA) is challenging to manage and comprises a significant health and economic burden. Many studies have been conducted in an attempt to define different clinical phenotypes that translate into biological endotypes, with the goal of tailoring treatment based on precision medicine. This review summarizes the current evidence for the treatments of SA, and in particular, the biologic treatments that are currently available: omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. We found only limited high-quality direct evidence regarding treatment with anti-IgE (omalizumab) in SA patients. Data regarding anti-interleukin (IL)-5 (mepolizumab, reslizumab and benralizumab) showed beneficial effects in severe eosinophilic asthma (SEA) with different levels of blood eosinophils used in clinical trials. Dupilumab, anti-IL-4/IL-13, was shown to be effective in SEA and is the only agent currently FDA-approved for the indication of oral corticosteroid dependent asthma, regardless of the blood eosinophil level. This review also summarizes the existing knowledge regarding the characteristics of the patient who may respond to the different therapies. As of today, more studies are needed to better understand the diverse mechanisms that underlie SA phenotypes. We have not yet adequately reached the goal of precision medicine. Additional studies are necessary in order to find novel surrogate markers that can predict the response to a specific biologic therapy, especially in patients who are oral corticosteroid dependent. In addition, efforts must be invested into research looking for new treatment options for patients with non-type-2 inflammation SA. Statement of novelty: we review the current evidence regarding tailored treatment therapies in SA, with a particular focus on the knowledge regarding patient selection for specific biologic treatments.

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Biologics for oral corticosteroid-dependent asthma

Allergy and Asthma Proceedings ◽

10.2500/aap.2020.41.200015 ◽

2020 ◽

Vol 41 (3) ◽

pp. 151-157

Author(s):

İnsu Yılmaz

Keyword(s):

Severe Asthma ◽

Oral Corticosteroid ◽

Real Life ◽

Severe Atopic Dermatitis ◽

Double Blind ◽

Eosinophilic Asthma ◽

Asthma Phenotype ◽

Severe Eosinophilic Asthma ◽

Term Administration

Background: Oral corticosteroid (OCS) dependent asthma is one of the severe asthma phenotypes that requires personalized treatment. Objective: To review the role of biologic treatments in OCS-dependent asthma. Methods: A nonsystematic review was performed of emerging multiple novel biologics for potential treatment of OCS-dependent asthma. Results: The serious adverse effects of OCS can be seen as a result of their regular long-term administration. Anti‐interleukin (IL) 5 (mepolizumab), anti‐IL-5R (benralizumab), and anti‐IL-4Rα (dupilumab) are the therapies of choice for OCS-dependent severe asthma. Results of studies showed the efficacy of mepolizumab, benralizumab, and dupilumab, especially in patients with the OCS-dependent severe eosinophilic asthma phenotype and with nasal polyps. Dupilumab may be the therapy of choice of monoclonal antibodies in cases of moderate-severe atopic dermatitis accompanied by OCS-dependent severe asthma. For reslizumab and omalizumab, placebo controlled double-blind studies conducted with OCS-dependent patient populations are needed. Conclusion: Biologics are effective in the “OCS-dependent asthma” phenotype as add-on therapy. It seems that chronic OCS use in OCS-dependent asthma will be replaced by biologic agents that specifically target type 2 inflammation, along with a much better safety profile. However, real-life studies that compare these biologics in OCS-dependent severe asthma are urgently needed.

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Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis

BMC Pulmonary Medicine ◽

10.1186/s12890-019-0952-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 11

Author(s):

Takanori Numata ◽

Katsutoshi Nakayama ◽

Hirofumi Utsumi ◽

Kenji Kobayashi ◽

Haruhiko Yanagisawa ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Severe Asthma ◽

Predictive Factors ◽

Systemic Corticosteroid ◽

Multivariate Logistic Regression Analysis ◽

Patient Characteristics ◽

Blood Eosinophil ◽

Eosinophilic Asthma ◽

Severe Eosinophilic Asthma ◽

Eosinophilic Chronic Rhinosinusitis

Abstract Background Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice. Objective To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma. Methods From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations. Results The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14). Conclusion Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.

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Corticosteroid tapering with benralizumab treatment for eosinophilic asthma: PONENTE Trial

ERJ Open Research ◽

10.1183/23120541.00009-2019 ◽

2019 ◽

Vol 5 (3) ◽

pp. 00009-2019 ◽

Cited By ~ 1

Author(s):

Andrew Menzies-Gow ◽

Jonathan Corren ◽

Elisabeth H. Bel ◽

Jorge Maspero ◽

Liam G. Heaney ◽

...

Keyword(s):

Adrenal Insufficiency ◽

Asthma Control ◽

Severe Asthma ◽

Maintenance Phase ◽

Phase Iii ◽

Eosinophilic Asthma ◽

Interleukin 5 ◽

Severe Eosinophilic Asthma ◽

Link Type ◽

Related Quality

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody approved in several countries for the add-on maintenance treatment of patients with severe eosinophilic asthma aged 12 years and older. In the 28-week Phase III ZONDA trial (ClinicalTrials.gov identifier: NCT02075255), benralizumab produced a median 75% reduction from baseline in oral corticosteroid (OCS) dosage (versus 25% for placebo) while maintaining asthma control for patients with OCS-dependent severe asthma. This manuscript presents the detailed protocol for the Phase IIIb PONENTE (ClinicalTrials.gov identifier: NCT03557307), a study that will build on the findings from ZONDA.As the largest steroid-sparing study undertaken in severe asthma, PONENTE has a faster steroid tapering schedule for prednisone dosages ≥7.5 mg·day−1 than previous studies, and it includes an evaluation of adrenal insufficiency and an algorithm to taper OCS dosage when prednisone dosage is ≤5 mg·day−1. It also has a longer maintenance phase to assess asthma control for up to 6 months after completion of OCS tapering.The two primary endpoints are whether patients achieve 100% reduction in daily OCS use and whether patients achieve 100% reduction in daily OCS or achieve OCS dosage ≤5 mg·day−1, if adrenal insufficiency prevented further reduction, both sustained over ≥4 weeks without worsening of asthma. Safety and change from baseline in health-related quality of life will also be assessed.PONENTE should provide valuable guidance for clinicians on tapering OCS dosage, including the management of adrenal insufficiency, following benralizumab initiation for the treatment of patients who are OCS-dependent with severe, uncontrolled eosinophilic asthma.

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