Clinical relevance of CompEx Asthma and impact on disease trajectory: benralizumab effect - PubMed (original) (raw)
Clinical relevance of CompEx Asthma and impact on disease trajectory: benralizumab effect
Clare Bolton et al. ERJ Open Res. 2026.
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, 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.
Methods: 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.
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 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.
Conclusions: 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.
Copyright ©The authors 2026.
Conflict of interest statement
Conflict of interest: S. Siddiqui has received funding for research from AstraZeneca and GSK and served on advisory boards/received advisory fees from GSK, AstraZeneca, Roche, Areteia Therapeutics, Owlstone Medical and Chiesi; he has received compensation for the development of continuing medical education (CME) from Medscape and serves on the ERS Science Council. N. Lugogo has received research funding from Sanofi, GSK, Genentech, Teva, Regeneron and AstraZeneca; has received consulting fees from AstraZeneca, GSK and Teva; has served on advisory boards for Sanofi, AstraZeneca, Genentech, Teva, Amgen and GSK; was a Spanish speaker at a national conference on allergy that was sponsored by AstraZeneca; and has received compensation for the development of CME content for IKH and Medscape. P. Akuthota has received consultancy fees and research support from AstraZeneca, GSK, Sanofi, Amgen and Connect Biopharma; has received research support from the American Partnership for Eosinophilic Disorders, the National Institutes of Health and Regeneron Pharmaceuticals; and has received royalties from UpToDate. C. Bolton, P. Barker and C.A. Da Silva are employees of, and own stock in, AstraZeneca. T. Bengtsson and S. Peterson are employees of StatMind, which received funding from AstraZeneca to complete the statistical analyses.
Figures
FIGURE 1
CompEx event types. SevEx: severe exacerbation; AWE: acute worsening event.
FIGURE 2
Morning/daytime (left) and evening/night-time (right) changes in a) peak expiratory flow (PEF), b) asthma symptoms (measured by the 6-item Asthma Control Questionnaire (ACQ-6)) and c) reliever medication use around the occurrence of a CompEx event in the combined CALIMA and SIROCCO trials. The three groups analysed were first severe exacerbation (SevEx) in the group that experienced SevEx only, first acute worsening event (AWE) in the group that experienced AWEs only and concomitant SevEx/AWE when it was the first event experienced in the group reporting mixed events. The shaded region shows the 95% confidence intervals.
FIGURE 3
Recovery following a CompEx event to mean baseline values of a) morning (left) and evening (right) peak expiratory flow (PEF), b) daytime (left) and night-time (right) asthma symptoms and c) daytime (left) and night-time (right) reliever medication use in the combined CALIMA and SIROCCO trials. The three groups analysed were first severe exacerbation (SevEx) in the group that experienced SevEx only, first acute worsening event (AWE) in the group that experienced AWEs only and concomitant SevEx/AWE when it was the first event experienced in the group reporting mixed events. Day 0 was the first day of the analysed event. The numbers at risk for each analysis group at each time point are shown under each graph.
FIGURE 4
Forced expiratory volume in 1 s (FEV1) trajectory over time in the overall population of the CALIMA and SIROCCO trials. Data were analysed according to the type of event recorded: severe exacerbation (SevEx) only throughout the trial; acute worsening event (AWE) only throughout the trial; mixed events, including concomitant SevEx/AWE, throughout the trial; no CompEx events (i.e. no SevEx or AWE or concomitant SevEx/AWE) throughout the trial; and any CompEx event throughout the trial (this included all patients in the SevEx only, AWE only and mixed groups).
FIGURE 5
Forced expiratory volume in 1 s (FEV1) trajectory over time in patients treated with benralizumab or placebo in the combined CALIMA and SIROCCO trials. Data were analysed according to the type of event recorded: severe exacerbation (SevEx) only throughout the trial; acute worsening event (AWE) only throughout the trial; mixed events, including concomitant SevEx/AWE, throughout the trial; and no CompEx events (i.e. no SevEx or AWE or concomitant SevEx/AWE) throughout the trial. Q8W: once every 8 weeks.
FIGURE 6
a) Asthma Quality of Life Questionnaire (AQLQ) and b) 6-item Asthma Control Questionnaire (ACQ-6) trajectories over time in the overall population in the combined CALIMA and SIROCCO trials. Data were analysed according to the type of event recorded: severe exacerbations (SevEx) only throughout the trial; acute worsening events (AWE) only throughout the trial; mixed events, including concomitant SevEx/AWE, throughout the trial; no CompEx events (i.e. no SevEx or AWE or concomitant SevEx/AWE) throughout the trial; and any CompEx event throughout the trial (this included all patients in the SevEx only, AWE only and mixed groups).
FIGURE 7
a) Asthma Quality of Life Questionnaire (AQLQ) and b) 6-item Asthma Control Questionnaire (ACQ-6) trajectories over time among patients treated with benralizumab or placebo in the combined CALIMA and SIROCCO trials. Data were analysed according to the type of event recorded: severe exacerbation (SevEx) only throughout the trial; acute worsening event (AWE) only throughout the trial; mixed events, including concomitant SevEx/AWE, throughout the trial; and no CompEx events (i.e. no SevEx or AWE or concomitant SevEx/AWE) throughout the trial. Q8W: once every 8 weeks.
References
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