predictive signature of benralizumab response

Conditions: Asthma; Eosinophilic; Severe Asthma

Summary: the objective of the study is to establish the predictive value of early blood gene expression signature of benralizumab response associated with a significant reduction of the number of exacerbations in treated severe asthmatic patients. this trial is a french, multicenter and no-randomized trial. patients enrolled will be clinically followed for 16 months (the treatment period: 12 months and 1 month follow-up; 6 clinical visit on site and in phone call at 13 months)


Eligibility criteria:
inclusion criteria: * patients between 18 and 75 years old. * patients diagnosed with severe asthma (chung and al, eur respir j 2014), i.e.: * asthma requiring high doses of ics (\>1000 microgram per day of beclomethasone or equivalent) associated with laba and/or systemic corticosteroids to be controlled over one year, * and/or uncontrolled asthma despite the later medications, * and/or a controlled asthma worsening after decreasing medications, * documented historical reversibility of fev1 ≥12% and fev1 gain ≥ 200 milliliter * acq-7 score ≥ 1,5 at m0. * ≥ 3 exacerbations in the 12 months prior to screening visit m-1. * eosinophil blood count ≥ 0,3 g/l at inclusion visit or in the 12 months prior to the inclusion visit. if eosinophil blood count is ≥ 0,15 g/l and \< 0,3 g/l, an eosinophilic phenotype defined by at least 1 of the following criteria will be required: * fractional exhaled nitric oxide (feno) \> 25 ppm at inclusion visit or in the 12 months prior to the inclusion visit. * sputum eosinophils ≥ 3% at inclusion visit or in the 12 months prior to the inclusion visit. * patients who provide written informed consent prior to participation in the study exclusion criteria: * patients diagnosed with difficult-to-treat asthma and/or with uncontrolled asthma differential diagnosis according to the judgment of the investigator (e.g., vocal cord dysfunction, gastroesophageal reflux disease, granulomatous eosinophilic vasculitis, obstructive sleep apnea syndrome, hyperventilation syndrome, allergic broncho-pulmonary aspergillosis, carrington disease, dipnech, asthma/copd overlap syndrome). * non-adherent patients to inhaled treatment (ics + laba). * active smokers or former smokers exceeding 20 packs year. * exacerbation at inclusion visit m0. * active malignancy or malignancy in remission over less than 5 years. * active parasitic infection or parasitic infection in the past 24 weeks. * hypersensitivity to benralizumab or to any of the excipients of fasenra® (histidine, histidine hydrochloride monohydrate, trehalose dihydrate, polysorbate 20) * patients requiring other immunosuppressive and immunomodulator drugs * patients requiring other biotherapy than benralizumab, with or without french's marketing authorisation in severe asthma * patients requiring other biotherapy than benralizumab that affects the immune system * sars-cov2 infection * pregnancy, lactation, or patients with childbearing potential refusing efficient contraceptive method. * patients under psychiatric condition altering their comprehension and their ability to give informed consent. * patients already enrolled in a clinical interventional research. * patients not affiliated to a health insurance plan * patients under guardianship, curators or safeguard of justice

Keywords: severe asthma therapeutic monoclonal antibody personalized medicine transcriptomic biomarkers