Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma

Comberiati, Pasquale; McCormack, Katherine; Malka-Rais, Jonathan; Spahn, Joseph D.

doi:10.1016/j.jaip.2019.05.053

Cited by 26 publications

(20 citation statements)

References 34 publications

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“…Childhood asthma is a heterogeneous disease with several distinct clinical phenotypes, among which is a group of children with FEV 1 values of ≥100% of predicted when clinically stable . The finding of this phenotype of persistent asthma with high FEV1 values even in some children with severe asthma is of significant clinical relevance as these children are at greater risk of being under‐treated when compared to severe asthmatics with reduced FEV 1 values . As a few studies have attempted to understand the respiratory mechanisms underlying asthmatic children with normal lung function vs those with impaired lung function at baseline, we characterized the lung mechanical properties of these two asthma phenotypes.…”

Section: Discussionmentioning

confidence: 99%

“…5 Similarly, in a recent extensive cohort of uncontrolled severe asthmatics diagnosed by the ERS/ATS 2014 criteria, children had a mean FEV 1 of 85% of predicted, whereas adults had a mean FEV 1 of 59% of predicted. 6 Taken together, these studies highlight important differences in lung function between children and adults and emphasize the relative lack of correlation in children between asthma severity and FEV 1 . Further, these studies identify what appears to be a distinct phenotype of persistent asthma in children that is characterized by FEV 1 values of at least 100% of predicted.…”

Section: Introductionmentioning

confidence: 92%

“…It is now recognized that many children with persistent asthma have forced expiratory volume in 1 second (FEV 1 ) values well within the normal range . In earlier studies, 28%‐49% of asthmatic children had FEV 1 > 100% of predicted .…”

Section: Introductionmentioning

confidence: 99%

“…It is now recognized that many children with persistent asthma have forced expiratory volume in 1 second (FEV 1 ) values well within the normal range. [1][2][3][4][5][6] In earlier studies, 28%-49% of asthmatic children had FEV 1 > 100% of predicted. [1][2][3] In contrast, only 14.8% of 12,844 adults studied had FEV 1 values of >100% of predicted, and their mean FEV 1 was 75.6% of predicted.…”

Section: Introductionmentioning

confidence: 99%

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Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Comberiati

Spahn

Paull

et al. 2020

Clin Experimental Allergy

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Background Children with asthma, even those with severe persistent disease, can have forced expiratory volume in 1 second (FEV1) values ≥100% of predicted, while others have diminished FEV1. Objective We sought to characterize the lung mechanical properties underlying these two asthma phenotypes and the mechanisms explaining the paradox of severe asthmatic children, whom when clinically stable can have an FEV1 >100% of predicted, but during an acute bronchospastic episode can experience a life‐threatening asthma event. Methods Lung mechanics were evaluated in three groups of children: asthmatics with FEV1 ≥100% (HFEV1; n = 13), asthmatics with FEV1 ≤80% (LFEV1; n = 14) and non‐asthmatic controls (n = 10). A linear mixed model was used to examine the relationship between volume and static transpulmonary pressures obtained at total lung capacity (TLC); actual TLC %of predicted and flow; and static transpulmonary pressure and flow. Results HFEV1 asthmatics had larger airways (FEV1 z‐scores 1.12 vs −2.37; P < .05), greater lung volumes (mean % of predicted TLC 134.8% vs 109.6%; P < .05) and lower airway resistance (mean %of predicted Raw 101.9% vs 199.9%; P < .05) compared to the LFEV1 group. Moreover, HFEV1 asthmatics had significantly reduced elastic recoil pressure (pressure‐volume curve shifted upward and to the left) and higher lung compliance (0.21 vs 00.9 L/cm H2O; P < .05) compared to the LFEV1 group. The pressure‐flow curves revealed the LFEV1 group to have significantly increased resistance to flow in the upstream segment of the airways at all lung volumes studied compared to HFEV1. Conclusion and Clinical Relevance HFEV1 asthmatic children display distinct lung mechanical proprieties compared to their LFEV1 asthmatic peers. With loss of elastic recoil pressure, the HFEV1 group could generate normal FEV1 due to proportionally enlarged airways and reduced airway resistance, while airflow limitation in the LFEV1 is due to increased airway resistance. Loss of elastic recoil and interdependence during acute bronchoconstriction episodes may predispose the HFEV1 group to catastrophic reductions in airflow.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Comberiati

Spahn

Paull

et al. 2020

Clin Experimental Allergy

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“…По опубликованным данным, на 2017 г. в США соответствовали критериям назначения меполизумаба 20% среди больных тяжелой эозинофильной БА [36]. Результаты, представленные в 2019 г., указывают, что меполизумаб может быть назначен 48% взрослым больным, страдающим тяжелой БА с детства, и 60% -с ТЭБА, стартовавшей во взрослом возрасте [37].…”

Section: клинические исследования мзб при баunclassified

Successful management of severe bronchial asthma: the right choice of biologic therapy in properly selected patients

Фассахов

2019

Medicinskij sovet

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Severe asthma along with the impact on the quality of life of those suffering from this disease leads to significant medical and social damage. Studies of the last decade indicate the leading role of eosinophilic inflammation of the bronchi as the basis of the pathogenesis of the T2 phenotype of bronchial asthma, which led to the development of targeted therapy. The most effective in this direction were preparations of humanized monoclonal antibodies directed against the main pro-inflammatory cytokines involved in respiratory tract inflammation in bronchial asthma, one of the most significant among which is interleukin 5. Refinement of the definition of severe asthma, selection of these patients among patients with difficult to treat bronchial asthma allows to clearly determine the contingent with a predicted positive effect these highly effective drugs precision therapy. On clinical examples, the difference between difficult to treat and severe bronchial asthma is discussed. The stages of clinical trials of the preparation of monoclonal antibodies against interleukin 5 Mepolizumab are analyzed in detail, the search for effective prognostic biological markers available in normal practice, allowing to select patients suitable for the treatment of patients with severe eosinophilic bronchial asthma. The effectiveness of the approach based on the allocation of two threshold values of the number of eosinophils in the peripheral blood is convincingly confirmed by the results indicating a significant reduction in the number of exacerbations, improved of lung function and an increase of the quality of life in patients, including with steroiddependent bronchial asthma, obtained not only in randomized clinical studies, but also in studies in real clinical practice.

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Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

Lombardi,

Comberiati,

Ridolo

et al. 2024

Drugs

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Monoclonal antibodies targeting interleukin (IL)-5 pathways have revolutionized the treatment expectations for eosinophilic-associated conditions, particularly in patients with respiratory involvement. Mepolizumab (IL-5 antagonist monoclonal antibody), benralizumab (IL-5 receptor blocker monoclonal antibody), and reslizumab (IL-5 antagonist monoclonal antibody) have collectively contributed to the overall improvement of the disease burden in various conditions. Eosinophilic asthma currently boasts the most robust evidence across all age groups: all three biologics are approved for adults (aged ≥18 years); mepolizumab is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) also in children (aged ≥ 6 years), while bernalizumab was recently approved by the FDA for patients aged ≥6 years in the USA. In chronic rhinosinusitis with nasal polyps, subcutaneous mepolizumab is the only anti-IL-5 therapy approved so far and can be used in adult patients (aged ≥18 years). For eosinophilic esophagitis, conflicting evidence surrounds both mepolizumab, reslizumab, and benralizumab, leading to non-approval of these agents by the FDA/EMA. Recently, mepolizumab was approved for eosinophilic granulomatosis with polyangiitis patients aged ≥6 years or older and for hypereosinophilic syndrome adult patients. A phase III trial proving noninferiority of benralizumab versus mepolizumab in eosinophilic granulomatosis with polyangiitis has been recently published, while evidence on reslizumab is scant. Overall, current evidence on anti-IL-5 biologics for eosinophilic-associated disorders is mostly focused on adults, whereas data for individuals aged under 18 years and over 65 years are scarce, resulting in a lack of evidence, particularly regarding efficacy, for the use of anti-IL-5 agents in these specific patient populations. This review addresses high-quality evidence from randomized controlled trials and real-world post-marketing studies regarding the use of anti-IL-5 therapies for eosinophilic-associated disorders across all age groups, spanning childhood, adulthood, and older age.

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Proportion of Severe Asthma Patients Eligible for Mepolizumab Therapy by Age and Age of Onset of Asthma

Cited by 26 publications

References 34 publications

Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Lung mechanical properties distinguish children with asthma with normal and diminished lung function

Successful management of severe bronchial asthma: the right choice of biologic therapy in properly selected patients

Anti-IL-5 Pathway Agents in Eosinophilic-Associated Disorders Across the Lifespan

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