Late Breaking Abstract - Up-dosing of reslizumab in severe asthmatics with persistent sputum eosinophilia

<bold>Rationale:</bold> A subset of severe eosinophilic asthmatics (SEA) remains uncontrolled despite anti-IL-5 biologic which may be due to inadequate neutralisation of airway IL-5. <bold>Aim:</bold> To investigate whether sequential up-dosing of a weight-adjusted anti-IL-5 mAb (reslizumab) will decrease sputum eosinophils(sp-eos) and improve asthma control. <bold>Method:</bold> We conducted a prospective, single-centre, open-label, 52-weeks dose-escalation (DE) study (<ext-link>NCT04710134</ext-link>). SEA with sp-eos>3% after 16 weeks of standard dose (3mg/kg, iv, Q4W) underwent DE to 4 mg/kg after V6 (4 infusions) or 5 mg/kg after V10 (4 infusions). Sp-eos, cytokines, anti-eosinophil peroxidase (EPX) IgG, FEV1, and ACQ-5 were examined. <bold>Results:</bold> Ten SEA (53±16 yrs; 6F) started reslizumab at 3 mg/kg (V1). After 4 infusions (V6), 4 (40%) had sp-eos>3% and ACQ-5<1.5, while n=5 (sp-eos 16±11%) were DE to 4 mg/kg, and one to 5 mg/kg. Reslizumab reduced sp-eos, EPX, IL-5 and improved FEV1 at V14 (p<0.05), irrespective of dosing. Despite reduced sp-IL-5 after DE, 2/10 patients (20%) had sp-eos at V14 (>3%, Fig 1A). Reslizumab did not reduce sp-IL-13 or anti-EPX levels. At V14, anti-EPX IgG were elevated in 5/6 DE patients and significantly correlated with IL-13 (r=0.7; P=0.02, Fig 1D). <bold>Conclusion:</bold> A proportion of SEA may benefit from higher doses of anti-IL-5 mAb that allow normalisation of sputum eosinophils and IL-5. A subset remains symptomatic with evidence of sp-eos, IL-13, and anti-EPX IgG. <fig><object-id>erj;64/suppl_68/PA3943/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>