Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab

Clare Bolton; Tim Harrison; Njira Lugogo; Anne Fuhlbrigge; Ian Hirsch; Thomas Bengtsson; Stefan Peterson; Martin Sidaway; Esther Garcia Gil; Malin Fagerås; Carla A Da Silva

doi:10.1183/23120541.01025-2023

Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab

ERJ Open Res. 2024 Mar 18;10(2):01025-2023. doi: 10.1183/23120541.01025-2023. eCollection 2024 Mar.

Authors

Clare Bolton¹, Tim Harrison^{1

2}, Njira Lugogo³, Anne Fuhlbrigge⁴, Ian Hirsch⁵, Thomas Bengtsson⁶, Stefan Peterson⁶, Martin Sidaway⁷, Esther Garcia Gil⁸, Malin Fagerås⁹, Carla A Da Silva⁷

Affiliations

¹ BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
² Nottingham Respiratory NIHR BRC, University of Nottingham, Nottingham, UK.
³ Division of Pulmonary and Critical Care, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.
⁴ Pulmonary Sciences and Critical Care, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
⁵ Late-stage Vaccine and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁶ StatMind Statistical and Mathematical Modelling, Innovation and Design AB, Lund, Sweden.
⁷ Early Respiratory and Immunology Clinical Development, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
⁸ GMA Respiratory & Immunology, AstraZeneca, Barcelona, Spain.
⁹ BioPharmaceuticals Medical, AstraZeneca, Gothenburg, Sweden.

Abstract

Background: CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma.

Methods: This post hoc analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo. Annualised event rates were analysed using a negative binomial model. The impact of blood eosinophil count on treatment effect was assessed.

Results: Among patients with a blood eosinophil count ≥300 cells·µL^-1 (n=913), benralizumab reduced the annualised event rate versus placebo for CompEx (1.57 versus 2.57; risk ratio 0.61, 95% CI 0.53-0.70, p<0.001), SevEx (0.94 versus 1.55; risk ratio 0.60, 95% CI 0.52-0.70, p<0.001) and AWE (0.92 versus 1.57; risk ratio 0.59, 95% CI 0.48-0.72, p<0.001), with greater treatment effects observed for higher blood eosinophil counts. In patients with blood eosinophil count ≥300 cells·µL^-1, benralizumab was associated with shorter median event duration (CompEx: 10.5 days versus 17.0 days; SevEx: 10.0 days versus 15.0 days; AWE: 5.0 days versus 6.0 days).

Conclusions: Benralizumab reduced the risk of CompEx events with treatment effects similar to those for SevEx and AWEs across a range of blood eosinophil counts. Use of CompEx supports the evaluation of benralizumab and other novel drugs in clinical studies.