Effects of Anti-IL5 Biological Treatments on Blood IgE Levels in Severe Asthmatic Patients

Study Overview
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Brief Summary
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Real-life, observational, retrospective, multicenter study to evaluate the effects of anti-IL5 biological treatments on blood total IgE Levels in atopic patients with severe eosinophilic asthma.

Detailed Description
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Severe asthma, i.e. asthma that is not controlled despite maximal optimized therapy and/or that worsens when high dose treatment is decreased (GINA guidelines - available at https://ginasthma.or), is a major unmet medical need. Major advances in the management of severe asthma occurred in the past few years due to the new targeted biological therapies. Mepolizumab and Benralizumab are humanized monoclonal antibodies able to block interleukin (IL)-5 and the receptor for IL-5, respectively. These biological treatments block the eosinophilic driven inflammation. The effects of these treatments on an other key effector molecule of the T2-immune response, i.e. IgE, is virtually unknown. To explore this issue, we set up a real life, observational, retrospective, multicenter study. The study will enroll patients with severe eosinophilic asthma already treated with Mepolizumab or Benralizumab. The following variable will be collected before the the biological treatment and at 4±2 months after the initiation of the pharmacological regimen: demographic data age of onset of asthma smoking habit concomitant pharmacological regimens number of asthma exacerbations since last visit concomitant diseases (particularly gastroesophageal reflux, nasal polyposis, atopic dermatitis, obesity, anxiety-depressive syndrome). White Blood Cell Count and Differential (and in particular the levels of total leucocytes, lymphocytes, eosinophils and basophils) Lung function tests (spirometry)

Official Title
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Effects of Anti-IL5 Biological Treatments of Total Blood IgE Levels in Severe Asthmatic Patients: Real-life Retrospective Multicenter Observational Study

Conditions
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Asthma, Asthma; Eosinophilic

Intervention / Treatment
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* Diagnostic Test: Total IgE
* Diagnostic Test: Blood cell counts
* Diagnostic Test: Asthma control assessment
* Diagnostic Test: lung function tests


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: atopy severe eosinophilic asthma (according to GINA guideline - available at https://ginasthma.org) patients treated with monoclonal antibody anti IL-5 (Mepolizumab) or with IL-5 anti-receptor monoclonal antibody (Benralizumab). stable asthma (free from asthma exacerbation for at least 8 weeks) Exclusion Criteria: asthma exacerbation in last 8 weeks patients treated for COPD
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mepolizumab group<br>atopic patients with severe eosinophilic asthma treated with anti-IL-5 monoclonal antibody (Mepolizumab) | Diagnostic Test: Total IgE<br>* Levels of total IgE before biological treatments and at 4±2 months of treatments<br>Diagnostic Test: Blood cell counts<br>* White Blood Cell Count and Differential (and in particular the levels of total leucocytes, lymphocytes, eosinophils and basophils)<br>Diagnostic Test: Asthma control assessment<br>* Levels of asthma control assessed by asthma control questionnaire (ACT) before initiation of biological treatments and at 4± months of treatments<br>Diagnostic Test: lung function tests<br>* Lung function tests performed before initiation of biological treatments and at 4± months of treatments<br>|
| Benralizumab group<br>atopic patients with severe eosinophilic asthma treated with anti-IL5 receptor monoclonal antibody (Benralizumab) | Diagnostic Test: Total IgE<br>* Levels of total IgE before biological treatments and at 4±2 months of treatments<br>Diagnostic Test: Blood cell counts<br>* White Blood Cell Count and Differential (and in particular the levels of total leucocytes, lymphocytes, eosinophils and basophils)<br>Diagnostic Test: Asthma control assessment<br>* Levels of asthma control assessed by asthma control questionnaire (ACT) before initiation of biological treatments and at 4± months of treatments<br>Diagnostic Test: lung function tests<br>* Lung function tests performed before initiation of biological treatments and at 4± months of treatments<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IgE levels in mepolizumab group | To evaluate total IgE levels (kU/l) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months after initiation of anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total leucocytes in mepolizumab group | To evaluate total leucocytes (number of cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| Eosinophils (number) in mepolizumab group | To evaluate the number of blood eosinophils (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| Eosinophils (%) in mepolizumab group | To evaluate the percentage of blood eosinophils (%) total blood white cells in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| Basophils (number) in mepolizumab group | To evaluate the number of blood basophils (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| Basophils (%) in mepolizumab group | To evaluate the percentage of blood basophils (%) to totale white blood cells in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| lymphocytes (number) in mepolizumab group | To evaluate the number of blood lymphocytes (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| Lymphocytes (%) in mepolizumab group | To evaluate the percentage of blood lymphocytes (%) to total white cells in atopic patients with severe eosinophilic asthma at 4 ± 2 months from the start of treatment with anti-IL5 monoclonal antibody Mepolizumab | 4±2 months | 
| IgE levels in Benralizumab group | To evaluate total IgE levels (kU/l) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Total leucocytes in Benralizumab group | To evaluate total leucocytes (number of cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab compared to the pretreatment value | 4±2 months | 
| Eosinophils (number) in Benralizumab group | To evaluate the number of blood eosinophils (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Eosinophils (%) in Benralizumab group | To evaluate the percentage of blood eosinophils (%) total blood white cells in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Basophils (number) in Benralizumab group | To evaluate the number of blood basophils (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Basophils (%) in Benralizumab group | To evaluate the percentage of blood basophils (%) to totale white blood cells in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Lymphocytes (number) in Benralizumab group | To evaluate the number of blood lymphocytes (cell/µl) in atopic patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| Lymphocites (%) in Benralizumab group | To evaluate the percentage of blood lymphocytes (%) to total white cells in atopic patients with severe eosinophilic asthma at 4 ± 2 months from the start of treatment with Benralizumab | 4±2 months | 
| respiratory function (FEV1 - liter) in Mepolizumab group | To evaluate FEV1 (liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (FEV1 - %) in Mepolizumab group | To evaluate FEV1 (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (vital capacity - liter) in Mepolizumab group | To evaluate vital capacity (VC - liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (vital capacity - %) in Mepolizumab group | To evaluate VC (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (forced vital capacity - liter) in Mepolizumab group | To evaluate forced vital capacity (FVC - liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (forced vital capacity - % predicted) in Mepolizumab group | To evaluate FVC (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (FEV1/FVC ratio) in Mepolizumab group | To evaluate FEV1/FVC ratio in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab compared to the pretreatment value. | 4±2 months | 
| respiratory function (FEV1/VC ratio) in Mepolizumab group | To evaluate FEV1/VC ratio in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| respiratory function (FEV1 - %) in Benralizumab group | To evaluate FEV1 (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (FEV1 - lier) in Benralizumab group | To evaluate FEV1 (liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (FVC - liter) in Benralizumab group | To evaluate FVC (liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (FVC - %) in Benralizumab group | To evaluate FVC (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (VC - liter) in Benralizumab group | To evaluate VC (liter) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (VC - %) in Benralizumab group | To evaluate VC (% predicted) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| respiratory function (FEV1/FVC ratio) in Benralizumab group | To evaluate FEV1/VC ratio in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab compared to the pretreatment value. | 4±2 months | 
| respiratory function (FEV1/VC ratio) in Benralizumab group | To evaluate FEV1/FVC ratio in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| Fractional exhaled nitric oxigen (FeNO) in Mepozumab group | To evaluate FeNO (ppb) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Mepolizumab | 4±2 months | 
| Fractional exhaled nitric oxigen (FeNO) in Benralizumab group | To evaluate FeNO (ppb) in patients with severe eosinophilic asthma at baseline and at 4 ± 2 months from the start of treatment with Benraluzumab | 4±2 months | 
| Asthma control test in Mepolizumab group | To evaluate asthma control test (ACT) in patients with severe eosinophilic asthma at baseline and at baseline and at 4 ± 2 months from the start of Mepolizumab | 4±2 months | 
| Asthma control test in Benralizumab group | To evaluate asthma control test (ACT) in patients with severe eosinophilic asthma at baseline and at baseline and at 4 ± 2 months from the start of Benralizumab | 4±2 months | 
| correlation between eosinophils and total IgE | To evaluate the correlations (Pearson correlation coefficient) between the change in total eosinophil counts and IgE levels in patients treated with Mepolizumab or Benralizumab. | 4±2 months | 
| correlation between total IgE and lung function | To evaluate the correlations (Pearson correlation coefficient) between the change in total IgE levels and in functional parameters (FEV1, FVC and VC) in patients treated with Mepolizumab or Benralizumab. | 4±2 months | 
| correlation between total IgE and asthma control | To evaluate the correlations (Pearson correlation coefficient) between the change in total IgE levels and the change of asthma control (measured by asthma control test - ACT) in patients treated with Mepolizumab or Benralizumab. | 4±2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IgE, Eosinophils, Mepolizumab, Benralizumab, Severe Asthma