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

doi:10.1016/j.jaip.2022.12.004

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

J Allergy Clin Immunol Pract. 2023 Mar;11(3):885-895.e13. doi: 10.1016/j.jaip.2022.12.004. Epub 2022 Dec 23.

Collaborators

Australian Mepolizumab Registry Investigators:
Melissa Baraket, Philip Bardin, Jeffrey J Bowden, Simon Bowler, Jimmy Chien, Li Ping Chung, Christopher Grainge, Nicholas Harkness, Zinta Harrington, Christine Jenkins, Gregory P Katsoulotos, Vanessa M McDonald, Joy Lee, Matthew Peters, Helen K Reddel, Paul N Reynolds, Pathmanathan Sivakumaran, John W Upham, Peter A B Wark

Affiliations

¹ Clinical Management Group, Woolcock Institute of Medical Research, Sydney, NSW, Australia.
² Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia.
³ School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia.
⁴ Immunology and Allergy Unit, Campbelltown Hospital, Sydney, NSW, Australia; School of Medicine, Western Sydney University, Sydney, NSW, Australia.
⁵ Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia; Department of Thoracic Medicine, Frankston Hospital, Melbourne, VIC, Australia.
⁶ Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW, Australia; Department of Thoracic Medicine, St Vincent's Clinic, Sydney, NSW, Australia.
⁷ Department of Thoracic Medicine, Concord Hospital, Sydney, NSW, Australia.
⁸ Allergy, Asthma and Clinical Immunology Clinic, Alfred Health, Melbourne, VIC, Australia.
⁹ Allergy, Asthma and Clinical Immunology Clinic, Alfred Health, Melbourne, VIC, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁰ Respiratory Department, St Vincent's Hospital, Melbourne, VIC, Australia.
¹¹ Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia; School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia. Electronic address: peter.gibson@health.nsw.gov.au.

PMID: 36572182
DOI: 10.1016/j.jaip.2022.12.004

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenal Cortex Hormones / therapeutic use
Anti-Asthmatic Agents* / therapeutic use
Asthma* / diagnosis
Asthma* / drug therapy
Asthma* / epidemiology
Australia / epidemiology
Comorbidity
Humans
Nasal Polyps* / drug therapy
Nasal Polyps* / epidemiology
Obesity / drug therapy
Phenotype
Pulmonary Eosinophilia* / drug therapy
Pulmonary Eosinophilia* / epidemiology
Treatment Outcome

Substances

mepolizumab
Anti-Asthmatic Agents
Adrenal Cortex Hormones