Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma

Vicky Kritikos; Erin S. Harvey; Sean Stevens; Constance H. Katelaris; David Langton; Janet Rimmer; Claude S. Farah; Andrew Gillman; Mark Hew; Naghmeh Radhakrishna; Dennis Thomas; Peter G. Gibson; Australian Mepolizumab Registry Investigators; Jeffrey J. Bowden; Zinta Harrington

doi:10.1016/j.jaip.2022.12.004

Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma

Vicky Kritikos, Erin S. Harvey, Sean Stevens, Constance H. Katelaris, David Langton, Janet Rimmer, Claude S. Farah, Andrew Gillman, Mark Hew, Naghmeh Radhakrishna, Dennis Thomas, Peter G. Gibson, Australian Mepolizumab Registry Investigators, Jeffrey J. Bowden, Zinta Harrington

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice.

Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA.

Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed.

Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype.

Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Original language	English
Pages (from-to)	885-895.e13
Number of pages	24
Journal	Journal of Allergy and Clinical Immunology: In Practice
Volume	11
Issue number	3
Early online date	23 Dec 2022
DOIs	https://doi.org/10.1016/j.jaip.2022.12.004
Publication status	Published - Mar 2023

Keywords

Comorbidity
Eosinophilic inflammation
Mepolizumab
Phenotype
Severe eosinophilic asthma

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaip.2022.12.004Licence: In Copyright

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Kritikos, V., Harvey, E. S., Stevens, S., Katelaris, C. H., Langton, D., Rimmer, J., Farah, C. S., Gillman, A., Hew, M., Radhakrishna, N., Thomas, D., Gibson, P. G., Australian Mepolizumab Registry Investigators, Bowden, J. J., & Harrington, Z. (2023). Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma. Journal of Allergy and Clinical Immunology: In Practice, 11(3), 885-895.e13. https://doi.org/10.1016/j.jaip.2022.12.004

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title = "Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma",

abstract = "Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.",

keywords = "Comorbidity, Eosinophilic inflammation, Mepolizumab, Phenotype, Severe eosinophilic asthma",

author = "Vicky Kritikos and Harvey, {Erin S.} and Sean Stevens and Katelaris, {Constance H.} and David Langton and Janet Rimmer and Farah, {Claude S.} and Andrew Gillman and Mark Hew and Naghmeh Radhakrishna and Dennis Thomas and Gibson, {Peter G.} and {Australian Mepolizumab Registry Investigators} and Melissa Baraket and Philip Bardin and Bowden, {Jeffrey J.} and Simon Bowler and Jimmy Chien and Chung, {Li Ping} and Christopher Grainge and Nicholas Harkness and Zinta Harrington and Christine Jenkins and Katsoulotos, {Gregory P.} and McDonald, {Vanessa M.} and Joy Lee and Matthew Peters and Reddel, {Helen K.} and Reynolds, {Paul N.} and Pathmanathan Sivakumaran and Upham, {John W.} and Wark, {Peter A.B.}",

year = "2023",

month = mar,

doi = "10.1016/j.jaip.2022.12.004",

language = "English",

volume = "11",

pages = "885--895.e13",

journal = "Journal of Allergy and Clinical Immunology: In Practice",

issn = "2213-2198",

publisher = "American Academy of Allergy, Asthma and Immunology",

number = "3",

}

Kritikos, V, Harvey, ES, Stevens, S, Katelaris, CH, Langton, D, Rimmer, J, Farah, CS, Gillman, A, Hew, M, Radhakrishna, N, Thomas, D, Gibson, PG, Australian Mepolizumab Registry Investigators, Bowden, JJ & Harrington, Z 2023, 'Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma', Journal of Allergy and Clinical Immunology: In Practice, vol. 11, no. 3, pp. 885-895.e13. https://doi.org/10.1016/j.jaip.2022.12.004

TY - JOUR

T1 - Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma

AU - Kritikos, Vicky

AU - Harvey, Erin S.

AU - Stevens, Sean

AU - Katelaris, Constance H.

AU - Langton, David

AU - Rimmer, Janet

AU - Farah, Claude S.

AU - Gillman, Andrew

AU - Hew, Mark

AU - Radhakrishna, Naghmeh

AU - Thomas, Dennis

AU - Gibson, Peter G.

AU - Australian Mepolizumab Registry Investigators

AU - Baraket, Melissa

AU - Bardin, Philip

AU - Bowden, Jeffrey J.

AU - Bowler, Simon

AU - Chien, Jimmy

AU - Chung, Li Ping

AU - Grainge, Christopher

AU - Harkness, Nicholas

AU - Harrington, Zinta

AU - Jenkins, Christine

AU - Katsoulotos, Gregory P.

AU - McDonald, Vanessa M.

AU - Lee, Joy

AU - Peters, Matthew

AU - Reddel, Helen K.

AU - Reynolds, Paul N.

AU - Sivakumaran, Pathmanathan

AU - Upham, John W.

AU - Wark, Peter A.B.

PY - 2023/3

Y1 - 2023/3

N2 - Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

AB - Background: Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities are needed to inform clinical practice. Objective: To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA. Methods: Patients enrolled in the Australian Mepolizumab Registry (n = 309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin-exacerbated airway disease, asthma-chronic obstructive pulmonary disease overlap (ACO), fungal sensitization, and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed. Results: Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range: 47%-77%), maintenance oral corticosteroid use (dose reduction: 4.2-13.3 mg/d), and improved symptom control (Asthma Control Questionnaire-5 score: 1.9-2.4 point reduction) and lung function (mean: 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1 second). Peripheral blood eosinophils were reduced (mean: 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO, and fungal sensitization) modified the baseline phenotype. Conclusions: Mepolizumab treatment is associated with comparable clinical improvements in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

KW - Comorbidity

KW - Eosinophilic inflammation

KW - Mepolizumab

KW - Phenotype

KW - Severe eosinophilic asthma

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U2 - 10.1016/j.jaip.2022.12.004

DO - 10.1016/j.jaip.2022.12.004

M3 - Article

C2 - 36572182

AN - SCOPUS:85147210601

SN - 2213-2198

VL - 11

SP - 885-895.e13

JO - Journal of Allergy and Clinical Immunology: In Practice

JF - Journal of Allergy and Clinical Immunology: In Practice

IS - 3

ER -

Comorbidities Modify the Phenotype but Not the Treatment Effectiveness to Mepolizumab in Severe Eosinophilic Asthma

Abstract

Keywords

UN SDGs

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