Asthma; Eosinophilic
Conditions
Keywords
severe eosinophilic asthma, eosinophils, biological treatment, anti-interleukin(IL)-5, monoclonal antibody
Brief summary
This study is aimed at evaluation of the efficacy of mepolizumab 100 mg subcutaneously (SC) every 4 weeks in patients with severe eosinophilic asthma who have been treated for at least 12 months in several Polish allergy/asthma centres under the same protocol. Target population to be recruited has been set at 130 subjects from at least 6 asthma centers throughout the country. Data on demographics and asthma status will be collected using questionnaires at 3 time-points: pre-mepolizumab (pre-MEPO), after 24 weeks of mepolizumab (MEPO) and after 1 year of MEPO administration (some of the outcomes will be observed every 4 weeks). Primary endpoints will include: * Asthma exacerbations measured at qualification for the treatment (in the period of previous 52 weeks) and at the 24th and 52nd week of the treatment. * Oral Corticosteroids use dose (documented at qualification for the treatment and at the 24th and 52nd week of the treatment).
Detailed description
This study is aimed at evaluation of the efficacy of mepolizumab 100 mg SC every 4 weeks in patients with severe eosinophilic asthma who have been treated for at least 12 months in several Polish allergy/asthma centres under the same protocol. Retrospective multicentre observational study will involve 130 patients with severe eosinophilic asthma (SEA) who have been treated in six Severe Asthma Treatment Centres (SATCs) in Poland. In each SATC all data available in the program questionnaires will be transferred to the Study Data Sheet (questionnaire), and will be send to the study coordinator within 5 months from the study beginning The start-up meeting including partners from all centres involved will be organized to discuss the study protocol and to unify data collection The evaluation parameters (exacerbations rate, OCS dose) will be analysed at least at three time points: pre-MEPO, after 24 weeks of MEPO and after 1 year of MEPO administration (some of the outcomes will be observed every 4 weeks, for the details see 'study endpoints' section). In addition the following parameters which are available in patients' records will be analysed: * 5-item asthma control questionnaire (ACQ-5) score (measured at qualification for the treatment and every 4 weeks thereafter) * Asthma quality of life questionnaire (AQLQ) score (measured at qualification for the treatment and every 4 weeks thereafter) * Pre-bronchodilator FEV1 (measured at qualification for the treatment and every 4 weeks thereafter) Research activities will include: * collecting raw data from the clinical centres (paper version) and constructing a raw dataset (digital version), * data cleaning, computation of variables, * statistical analysis typical for pre-post study design (the statistical analysis will be outsourced to the specialized private institute). Clinical improvements observed at 24 weeks and at 52 weeks of treatment with Mepolizumab will be referred to the following characteristics of patients at baseline: * demographics, * presence of comorbidities including the atopic status, * concomitant pharmacotherapy, * clinical status, * eosinophilia. We will control for mepolizumab use regarding dose, treatment duration and dosing frequency as well as for the safety profile based on the AEs reporting in the medical documentation. Data Source / Data Collection Patients recruited to the study had been treated with mepolizumab between December 2017 and December 2019.All the data planned to be used in the proposed study were systematically collected in the form of the clinical documentation (paper version) and will be transferred in the study centres into the study. Data Sheets. Collaborating Researchers (Severe Asthma Centres' Leaders) will provide the data input into the dedicated online questionnaire. Study Population 130 Patients who were treated with mepolizumab in six severe-asthma clinics in Poland between December 2017 and December 2019 . In the drug program in Poland it was mandatory to conduct the control examinations at the 24th and 52nd week of the treatment . In the proposed study we will use this information to evaluate study endpoints. Only patients who have been treated for at least 52 weeks are included into the study Variables concerning the primary endpoints * Asthma exacerbations measured at qualification for the treatment (in the period of previous 52 weeks) and at the 24th and 52nd week of the treatment. * Oral Corticosteroids use dose (documented at qualification for the treatment and at the 24th and 52nd week of the treatment) Variables concerning the secondary endpoints: * ACQ-5 score (measured at qualification for the treatment and every 4 weeks thereafter) * AQLQ score (measured at qualification for the treatment and every 4 weeks thereafter) * Pre-bronchodilator forced expiratory volume in 1 second (FEV1) (measured at qualification for the treatment and every 4 weeks thereafter) * Blood eosinophil counts (measured at qualification for the treatment and at the 24th and 52nd week of the treatment)
Interventions
BIOLOGICALMepolizumab given SC 100mg every 4 weeks between Dec 2017 and Dec 2019
Mepolizumab administered within the frame of a severe asthma treatment program financed by National Health Fund in Poland for patients fulfilling specific criteria of asthma severity.
Sponsors
Medical University of Lodz
GlaxoSmithKline
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\* The availability of the complete data * Duration of treatment with mepolizumab: ≥ 52 weeks * Satisfying the Polish drug programme inclusion criteria: * Age \>18 * Before treatment with mepolizumab (BSAT inclusion criteria): * High doses of inhaled corticosteroids (ICS) + one other controlling medication (i.e. LABA) * ≥2 exacerbations in the previous year * ≥350 eosinophil cells/microliter (µl) in the peripheral blood at the time of qualification or in the previous year * Pre-bronchodilator FEV1 \< 80%
Exclusion criteria
\* Duration of treatment with mepolizumab \< 52 weeks • Lack of complete data
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Exacerbations During 52 Weeks Preceding Treatment Initiation (as Assessed at Baseline) and at the 24th and 52nd Week of the Treatment | Baseline (before mepolizumab initiation); week 24; week 52 | Data as transferred from the treatment program questionnaires to the Study Data Sheet. Asthma exacerbations, defined according to the Polish drug programme, is the worsening in asthma requiring (1) use of systemic corticosteroids or (2) increase in dose of OCS for more than 3 days in case of patients who are chronically treated with OCS. |
| Number Patients Requiring Treatment With Oral Corticosteroids (OCS) at a Chronic Basis (Documented at Qualification for the Treatment and at the 24th and 52nd Week of the Treatment) | Baseline (before mepolizumab initiation); week 24; week 52 | Data as transferred from the treatment program questionnaires to the Study Data Sheet |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ACQ-5 (Asthma Control Questionnaire 5-item) Score | Baseline (before mepolizumab initiation); week 24; week 52 | Asthma Control Questionnaire (ACQ) is the validated tool aimed to measure the adequacy of asthma control and change in asthma control occurring either spontaneously or as a result of treatment. It is self-administered by patients and assesses asthma symptoms intensity and frequency (5 items) on a 7-point scale (0 through 6; 0=absence, 6= maximum intensity/frequency), with total score being the average of the questions. ACQ score ranges from 0 (minimum) to 6 (maximum). A score of 1.5 or more indicates that a patient has inadequate asthma control. Difference in score of 0.5 or greater is considered clinically important (MCID, minimal clinically important difference). |
| AQLQ (Asthma Quality of Life Questionnaire) Score | Baseline (before mepolizumab initiation); week 24; week 52 | Asthma Quality of Life Questionnaire (AQLQ) is a disease-specific tool covering both physical and emotional impact of asthma upon the affected subjects' quality of life. This questionnaire has 4 domains: symptoms, activity limitation, emotional function, and environmental stimuli. The AQLQ has been validated in 2 variants: a standard AQLQ consisting of 32 items and a mini-AQLQ containing 15 items. In the national severe asthma treatment program in Poland a 15-item AQLQ is used, as per National Health Fund requirements. Items are scored on a 7-point Likert scale, with score 1 representing maximal impairment and the value of 7 attributed to "no impairment". The total score is calculated as a mean value of all items (a sum of scores divided by 15). A change of \>0.5 points is considered clinically significant. Score below 5 indicates considerable lowering of quality of life in an asthmatic subject and is one of the conditions for inclusion into the reimbursed treatment program. |
| Pre-bronchodilator FEV1 | Baseline (before mepolizumab initiation); week 24; week 52 | Pre-bronchodilator FEV1 (forced expiratory volume in 1 second) is a key indicator in lung funtion testing, measuring the volume of air exhaled from the lungs in the first second of a maximum forced exhalation. FEV1 is commonly used to diagnose and monitor obstructive lung diseases, including asthma. Values below 80% of the predicted value (calculated individually using basing on subject's age, sex, height, weight and ethnicity) indicates narrowing of the airways. |
| Blood Eosinophil Counts | Baseline (before mepolizumab initiation); week 24; week 52 | Data as transferred from the treatment program questionnaires to the Study Data Sheet |
Countries
Poland
Contacts
PRINCIPAL_INVESTIGATORMarcin Kurowski, MD, PhD
Medical University of Lodz
Participant flow
Recruitment details
Patients having received mepolizumab 100 mg SC every 4 weeks for at least 12 months in six severe-asthma clinics in Poland between December 2017 and December 2019
Pre-assignment details
Not applicable. A uniform, single treatment group throughout the study. No wash-out or run-in periods.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Age | 56.6 years |
| Region of Enrollment Poland | 106 Participants |
| Sex: Female, Male Female | 77 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 106 |
| other Total, other adverse events | 1 / 106 |
| serious Total, serious adverse events | 1 / 106 |
Outcome results
None listed