Anti-Interleukin-5 (IL5) Monoclonal Antibody (MAb) in Prednisone-dependent Eosinophilic Asthma

Study design Blinded placebo-controlled sequential clinical trial of 4 monthly doses of intravenously administered reslizumab. The study will include two periods: Period 1: After establishing the minimum dose of prednisone to observe sputum eosinophils ≥3% and blood eosinophils ≥300/µL, all subjects will receive 2 infusions (once monthly) of matching placebo. Period 2: All subjects will then receive 4 infusions (once monthly) of reslizumab 3mg/kg. Methods 15 patients (all of whom had sputum eosinophils ≥3% and blood eosinophils ≥300/µL) who were previously treated with S/C100 mg mepolizumab for at least 6 months, with the last dose at least 4 months before entering the study, will be invited to participate in the study. Since discontinuing mepolizumab, these patients would have been re-established on their maintenance dose of daily prednisone + high doses of inhaled corticosteroids (ICS) and long acting beta agonist (LABA). Baseline measurements of blood and sputum eosinophils, spirometry, symptoms (ACQ), and immune cells in blood and sputum (ILC2 cells, CD4 + cells, CD8+ cells, CD34+ Eo/B progenitor cells) will be enumerated by flow cytometry, and measures of local autoimmunity, using our established protocols at the start of Period 1 (baseline measurement). They will then receive 2 infusions of placebo at monthly intervals, and measurements will be repeated at the end of Period 1 (post-placebo measurement). The subjects will then receive by 4 infusions of 3 mg/kg reslizumab at monthly intervals. At the end of the 4 months, these measurements will be repeated (post-reslizumab measurement).