Clinical relevance of CompEx Asthma and impact on disease trajectory: benralizumab effect

Abstract Background Severe exacerbations (SevEx), the typical endpoint when evaluating asthma therapies, may provide incomplete assessment, as it relies on patient perception of disease and physician action. CompEx includes SevEx and acute worsening events (AWEs; evaluated from e-diary entries using: deterioration in peak expiratory flow PEF; reliever medication use; worsening asthma symptoms) and should provide more objective assessment. The correlation of CompEx event subtypes—SevEx only, AWE only, or mixed SevEx/AWE—with disease trajectory and effect of benralizumab in SIROCCO and CALIMA were evaluated. Methods Post hoc analysis of patients (≥12 years) with severe, uncontrolled asthma treated with benralizumab 30 mg or placebo every 8 weeks. PEF, symptoms and reliever medication use around CompEx event subtype occurrence, forced expiratory volume in 1 s (FEV 1 ) trajectories and patient-reported outcomes were evaluated. Results 953 patients were included (benralizumab, n=465; placebo, n=488). Greater increases in asthma symptoms and reliever medication use, declines in PEF and slower return to baseline were seen around AWE or mixed SevEx/AWE than SevEx, according to treatment utilisation. Overall, patients without a CompEx event had the best FEV 1 trajectory and patient-reported outcomes versus those with any CompEx event. Benralizumab reduced SevEx risk in patients experiencing SevEx only or mixed SevEx/AWEs; no effect was seen in patients with AWE only. Conclusions CompEx includes SevEx and AWEs, both of which are clinically relevant events, providing a more comprehensive assessment of asthma worsening versus SevEx alone. AWEs are particularly important contributors to poor asthma outcomes and should not be ignored when evaluating treatments.