Asthma is a chronic disease characterized by inflammation and obstruction of the airways. Identification of the mechanisms of action of corticosteroids has made it possible to define the type 2 inflammation present in nearly 80% of patients with asthma. Monoclonal antibodies (MAb) in severe asthma target type-2 inflammation. Mepolizumab is a humanized IgG1 (immunoglobulin gamma-1) kappa subclass monoclonal antibody directed specifically against interleukin 5 (IL-5). It acts specifically on eosinophil homeostasis, with IL-5 being a key interleukin in eosinophil maturation. The investigators propose to measure the concentrations of mepolizumab in the serum of asthmatic patients treated with this mAb. The investigators hypothesize that the individual pharmacokinetics (PK) of mepolizumab may differ between clinical responders and non-responders.
Asthma is a chronic disease characterized by inflammation and obstruction of the airways. Understanding the biological effects of the corticosteroids allowed to identify and to define the type 2 inflammation present in nearly 80% of patients with asthma. Monoclonal antibodies (MAb) in severe asthma target type-2 inflammation. Mepolizumab is a humanized IgG1 kappa subclass monoclonal antibody directed specifically against interleukin 5 (IL-5). It acts specifically on eosinophil homeostasis, since IL-5 is a key interleukin in eosinophil maturation. Poor MAb responses can hypothetically arise in situations of poor treatment compliance. And after excluding the latter, several biological mechanisms have been mentioned: i) insufficient bioavailability of the MAb to reach the eosinophils of the bronchial compartment; ii) he development of autoimmunity with the formation of circulating immune complexes; and iii) immunization against mepolizumab, with the formation of neutralizing anti-drug antibodies (ADA). ADA were detected in up to 20% of a treated population and were rarely neutralizing. Interestingly, these ADA could also be detected in naïve populations, suggesting a possible cross-immunization related to previous exposure to MAbs and/or to insufficient assay specificity. In any case, all three possibilities have a common outcome, i.e. decreased circulating concentrations of the MAb in the blood. The investigators propose to measure the concentrations of mepolizumab in the serum of asthmatic patients treated with this mAb. The investigators hypothesize that the individual pharmacokinetics (PK) of mepolizumab may differ between clinical responders and non-responders.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
50
blood sample taken to measure serum mepolizumab concentration at baseline, 1 month and 6 months during study follow-up
university Hospital of Montpellier
Montpellier, France, France
University Hospital of Tours
Tours, France, France
Change in Mepolizumab serum concentration
The primary outcome is the change in trough concentration of mepolizumab in serum at 1-month post-enrolment. Mepolizumab serum concentration will be determine by ELISA
Time frame: 1 month
Mepolizumab serum concentration
Mepolizumab serum concentration will be determine by ELISA.
Time frame: 6 months
Complete blood cell count at 1 month
comparison of number and % of eosinophils, basophils, neutrophils between responders and non-responders at baseline and 1-month
Time frame: 1 month
Complete blood cell count at 6 months
comparison of number and % of eosinophils, basophils, neutrophils between responders and non-responders for the six-month follow-up period
Time frame: 6 months
Comparison of lung function by airway obstruction
To describe the degree of airway obstruction, forced expiratory volume in one second (FEV1) and forced vital capacity will be measured using spirometry. The quantitative variables FEV1 and FEV1/FVC (Forced Vital Capacity) will be compared between responders and non-responders for the six-month follow-up period
Time frame: 6 months
Comparison of asthma control by ACQ-6 score
Asthma control in terms of symptoms will be assessed by the six-item Asthma Control Questionnaire (ACQ-6). The ACQ-6 scores will be compared between responders and non-responders for the six-month follow-up period. Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is the mean of the responses. A score of 1.5 or more on the 6-item Asthma Control Questionnaire (ACQ-6) indicates that a patient has inadequate asthma control.
Time frame: 6 months
Comparison of chronic rhinosinusitis by SNOT-22 score
The sino-nasal outcomes for chronic rhinosinusitis will be assessed by the 22-item sino-nasal outcome test (SNOT-22). The SNOT-22 scores will be compared between responders and non-responders for the six-month follow-up period. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110. Higher scores indicate poorer outcomes.
Time frame: 6 months
Comparison of exacerbation rate
Number, dates, and severity of exacerbations as defined by the Global Asthma Initiative (GINA) will be collected throughout the follow-up period. The number of exacerbations, the exacerbations rate and the number of days not exacerbating will be compared between responders and non-responders.
Time frame: 6 months
Number of days alive and not exacerbating
Time frame: 6 months
Comparison of change in oral corticosteroid
Oral corticosteroid use will be collected throughout the follow-up period. The % decrease of the initial corticosteroid therapy will be compared between responders and non-responders at 6 months.
Time frame: 6 months
Presence/absence of a >50% reduction in exacerbation rate
Time frame: 6 months
Presence/absence of monoclonal antibody switching
Time frame: 6 months
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