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

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, a composite outcome that includes SevEx and acute worsening events (AWEs) (evaluated from e-diary entries using deterioration in peak expiratory flow (PEF), reliever medication use and worsening asthma symptoms), 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 the SIROCCO and CALIMA trials were evaluated.

This was a post hoc analysis of patients (aged ≥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 (FEV₁) trajectories and patient-reported outcomes were evaluated.

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 and mixed SevEx/AWE than SevEx, according to treatment utilisation. Overall, patients without a CompEx event had the best FEV₁ trajectory and patient-reported outcomes, compared with 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.

CompEx includes SevEx and AWEs, both of which are clinically relevant events, providing a more comprehensive assessment of asthma worsening than SevEx alone. AWEs are particularly important contributors to poor asthma outcomes and should not be ignored when evaluating treatments.