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

Bolton, Clare ; Akuthota, Praveen ; Lugogo, Njira ; Barker, Peter ; Bengtsson, Thomas ; Peterson, Stefan LU ; Siddiqui, Salman and Da Silva, Carla A. (2026) In ERJ open research 12(1).
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... (More)

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 patientreported 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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
ERJ open research
volume
12
issue
1
article number
00486-2025
publisher
European Respiratory Society
external identifiers
  • scopus:105032904172
  • pmid:41736726
ISSN
2312-0541
DOI
10.1183/23120541.00486-2025
language
English
LU publication?
yes
additional info
Publisher Copyright: © The authors 2026.
id
6ce06787-9da0-4b48-94fe-d3b003ab31d6
date added to LUP
2026-05-13 15:44:30
date last changed
2026-08-21 05:56:17
@article{6ce06787-9da0-4b48-94fe-d3b003ab31d6,
  abstract     = {{<p>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 (FEV<sub>1</sub>) trajectories and patientreported 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 FEV<sub>1</sub> 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.</p>}},
  author       = {{Bolton, Clare and Akuthota, Praveen and Lugogo, Njira and Barker, Peter and Bengtsson, Thomas and Peterson, Stefan and Siddiqui, Salman and Da Silva, Carla A.}},
  issn         = {{2312-0541}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{European Respiratory Society}},
  series       = {{ERJ open research}},
  title        = {{Clinical relevance of CompEx Asthma and impact on disease trajectory : benralizumab effect}},
  url          = {{http://dx.doi.org/10.1183/23120541.00486-2025}},
  doi          = {{10.1183/23120541.00486-2025}},
  volume       = {{12}},
  year         = {{2026}},
}