Severe eosinophilic asthma with paradoxal worsening T2 bronchial inflammation despite sequencial treatment with mepolizumab and benralizumab

Biotherapies blocking IL-5 and IL-4 pathways allowed improvement in the treatment of eosinophilic asthma. We expose a clinical report of a paradoxal worsening of bronchial T2 inflammation after mepolizumab initiation. A switch for benralizumab did not led to clinical or inflammatory improvement A 32 years old patient without any respiratory history was diagnosed with severe asthma and nasal polyposis without aspirin sensitivity after an initial severe exacerbation. Phenotyping highlighted a polysensitivation (cat,dog,grass pollen, dust mites) and a marked type 2 inflammation with hypereosinophilia in blood (900/mm3) and sputum(3%), and high FeNO(40ppb). There was no bronchial obstruction with a FEV1 at 94%. Asthma was uncontrolled despite high inhaled corticosteroids. A systemic oral corticosteroid therapy initiated after the first exacerbation could not be decreased under 30mg/day prednisolone. Mepolizumab 100mg/4W was introduced. Three months after mepolizumab initiation, we observed a paradoxal worsening with a FEV1 decrease (60%) and higher bronchial inflammation (FeNO up to 150ppb and sputum eosinophilia at 13%) despite oral corticosteroids continuation at the same posology. Blood eosinophilia was low. FEV1 and FeNO did not improve thereafter. Mepolizumab was interrupted after 5 injections and benralizumab was initiated 6 month later without any improvement This case reports a bronchial T2 inflammation worsening with persistant low blood eosinophilia under mepolizumab and oral steroids therapy. There was no improvement under benralizumab suggesting that blood eosinophilic depletion was associated with a lower eosinophilic bronchial infiltration