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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma; Asthma; Eosinophilic
• Intervention / Treatment: Diagnostic test: Total IgE; Diagnostic test: Blood cell counts; Diagnostic test: Asthma control assessment; Diagnostic test: lung function tests

Detailed Description

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)

• Study Type: Observational
• Enrollment (Actual): 130

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44124
    • Azienda Ospedaliero Universitaria Ferrara
  • Foggia, Italy
    • Professor of Respiratory Medicine Department of Medical and Surgical Sciences University of Foggia - Italy
  • Milan, Italy
    • UOC Pneumologia Ospedale L.Sacco - Polo Univestiario ASST Fatebenefratelli - Milano
  • Modena, Italy
    • Malattie dell' Apparato Respiratorio Dipartimento di Scienza Mediche e Chirurgiche Materni-Infantili e dell'Adulto. Azienda Ospedaliero Universitaria di Modena
  • Palermo, Italy
    • AOUP Giaccone Palermo, dipartimento PROMISE, Università di Palermo
  • Pordenone, Italy
    • S.C di Pneumologia Ospedale S. Maria degli Angeli AAS5 Friuli Occidentale
  • Reggio Emilia, Italy
    • Department of Medical Specialties, Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia-IRCCS
  • Verona, Italy
    • UOC Pneumologia Azienda Ospedaliera Univeristaria Integrata - Verona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

atopic patients with severe eosinophilic asthma treated with anti IL-5 (Mepolizumab) or anti IL5-receptor (Benralizumab) humanized monoclonal antibodies

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara
• Investigators: Principal Investigator: Marco Contoli, Prof, Università di Ferrara - Azienda Ospedaliero Universitaria di Ferrara

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 11, 2019
• Primary Completion (ACTUAL): October 1, 2020
• Study Completion (ACTUAL): November 1, 2020

Study Registration Dates

• First Submitted: November 15, 2019
• First Submitted That Met QC Criteria: November 27, 2019
• First Posted (ACTUAL): November 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: Mepolizumab; Benralizumab; Severe Asthma; Eosinophils; IgE
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia
• Other Study ID Numbers: 272/2019/Oss/AOUFe BIONIGE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No