Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting
Study Details
Study Description
Brief Summary
The goal of this exploratory and observational prospective study is to study the composition and phenotypes of blood leukocytes collected from asthmatic patients before and after instantiated treatment with the interleukin-5 neutralizing antibody mepolizumab. Comparisons will be made to leukocyte profiles in patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Asthma is a chronic inflammatory and obstructive condition affecting the airways. The disease is commonly associated with elevated blood eosinophils and tissue eosinophilia. Many aspects of the pathophysiological mechanisms and clinical symptoms are controlled by conventional therapies such as inhaled corticosteroids (ICS) and long acting β2 agonists. However, some patients remain clinically uncontrolled and need additional treatment such as direct targeting of eosinophil granulocytes by neutralizing the eosinophil-promoting cytokine interleukin 5 (IL5). Mepolizumab is a humanized monoclonal IL-5 neutralizing antibody that is used to treat patients with moderate-severe eosinophilic asthma. While a marked reduction of eosinophils is a key effect of mepolizumab, the exact mechanism of action is unknown. Apart from basophils, that also express the receptor for IL-5, other leukocytes are likely to be indirectly affected by the suppressed eosinophilia. In addition, it is largely unknown to what extent the few eosinophils remaining after anti-IL5 treatment differ from pre-treatment eosinophils.
The present study is a prospective observational asthma study that aims to use microscopic analysis to investigate the composition and subtypes of blood leukocytes collected before and after instantiated mepolizumab treatment. Comparisons are made to patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Asthma patients initiating Mepolizumab treatment Patients will be selected on the standard criteria used to select eligible asthma patients for mepolizumab treatment (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients may be included. Exclusion criteria: any infection |
Biological: Mepolizumab
Mepolizumab is administered by subcutaneous injection with guideline recommended patient selection and dosing for treatment of eosinophilic asthma.
Accordingly, the Mepolizumab treatment is given as add-on therapy to standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Other Names:
Drug: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Other Names:
|
| Asthma patients already on Mepolizumab treatment Patients that have been selected and given Mepolizumab treatment for > 4 months according to standard eligible and treatment regimen criteria (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients that have been on Mepolizumab treatment for > 4 weeks will be included. Exclusion criteria: any infections |
Biological: Mepolizumab
Mepolizumab is administered by subcutaneous injection with guideline recommended patient selection and dosing for treatment of eosinophilic asthma.
Accordingly, the Mepolizumab treatment is given as add-on therapy to standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Other Names:
Drug: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Other Names:
|
| Asthma patients without Mepolizumab treatment Inclusion: Asthma patients without any biological (antibody-based) treatment but on routine ICS and LABA treatment as part of their normal care. Exclusion criteria are any infections |
Drug: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Routine asthma treatment with inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA)
Other Names:
|
| Healthy non-asthmatic control subjects Exclusion criteria: previous history of lung disease, chronic inflammatory condition, or atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling |
Outcome Measures
Primary Outcome Measures
- Change in Blood Eosinophil Marker Expression [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Quantitative immunohistochemical analysis of eosinophil marker expression in blood leukocyte pellets
- Change in Blood Basophil Marker Expression [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Quantitative immunohistochemical analysis of basophil marker expression in blood leukocyte pellets
- Change in Blood Leukocyte Composition [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Immunohistochemical determination of the relative proportion (percent) of the leukocyte populations in blood leukocyte pellets
Secondary Outcome Measures
- Change in Blood T Lymphocyte Marker Expression [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets
- Change in Blood B Lymphocyte Marker Expression [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Quantitative immunohistochemical analysis of T lymphocyte marker expression in paraffin-embedded blood leukocyte pellets
- Leukocyte Total Cell Counts [Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment]
Routine hemacytometer total leukocyte cell counts
Other Outcome Measures
- Change in Forced Expiratory Volume in 1 second (FEV1) [Change from baseline at 4 weeks, and 4 months after initiated biological treatment.]
Spirometry: Forced Expiratory Volume, 1s; (FEV1).
- Change in Forced Vital Capacity (FVC) [Change from baseline at 4 weeks, and 4 months after initiated biological treatment.]
Spirometry: Forced Vital Capacity (FVC)
- Change in Exhaled FeNo [Before and 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment.]
Fractional exhaled NO will be measured at multiple flows
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinical diagnosis of asthma (the asthma patient arms)
-
Eligible for Mepolizumab treatment as per the country-specific prescribing information (the arms with Mepolizumab)
Exclusion criteria:
-
Any diagnosed infection (all arms)
-
Previous history of lung disease, chronic inflammatory condition, atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling (Healthy non-asthma control subjects)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Lung and Allergy Clinic, Skåne University Hospital (SUS) | Lund | Skane | Sweden | 22185 |
Sponsors and Collaborators
- Region Skane
- Lund University
Investigators
- Principal Investigator: Jonas Erjefält, Lund University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1072615