Abstract Introduction In severe asthma patients with frequent exacerbations, improvements observed after biologic initiation may reflect biologic effects, natural disease variability or concurrent non-biologic interventions. We hypothesised that a subgroup improves without biologics and aimed to identify features that distinguish patients who persistently exacerbate (truly need biologics) from those likely to improve under standard care. Methods Adult severe asthma patients were identified using the Clinical Practice Research Datalink linked to Hospital Episode Statistics for emergency visits and admissions. Consecutive 12-month windows were observed from study entry (latest of asthma diagnosis, first asthma prescription or eighteenth birthday). “Year 0” was the first year each patient met severe asthma criteria and had ≥3 systemic corticosteroid-treated exacerbations (biologic-eligible). Post-Year 0 exacerbation trajectories were identified using longitudinal k-means. The optimal cluster number (k = 3) panel of model fit statistics. Sensitivity analyses included using k = 4, lower eligibility threshold (≥2 exacerbations/year) and an alternative clustering approach (group-based trajectory modelling). Covariates included the highest blood eosinophil count, total inhaled corticosteroid (ICS) per interval and comorbidities. Results Among 10,078 biologic-eligible adults (median age 51 years; 71% female), we identified three exacerbation trajectories post-biologic eligible year. The remitting-stable (70%, n = 7,091) group showed marked exacerbation reduction in the first year and remained low thereafter. The chronic-frequent (20%, n = 1,960) group showed persistent frequent exacerbations (median 5/year). The refractory-frequent (10%, n = 1,018) group had very high, sustained systemic corticosteroid exposure (median 10 exacerbations/year) (Figure 1A). Findings were comparable with all three sensitivity analyses. Chronic-frequent patients had higher bronchiectasis prevalence than remitting-stable (8% versus 5%, p 0.001), but were similar in age, sex, and allergic comorbidities (rhinitis/eczema/hay fever). Blood eosinophils were higher in chronic-frequent patients (median 0.30 × 109/L) at Year 0 and during prior years (median 0.23 × 109/L in remitting-stable, 0.21 × 109/L in refractory-frequent, p 0.001) (Figure 1B). All groups had higher ICS doses in Year 0 than in years prior. Remitting-stable patients most frequently reduced their ICS dose post-Year 0, yet continued to improve in exacerbations (Figure 1C). Conclusion Over half of patients who met criteria for biologics improved to less than 3 exacerbations/year with usual care alone. Chronic frequent exacerbators had persistently elevated blood eosinophils (≥0.3 × 109/L) several years before biologic eligibility. At a population level, eosinophil counts may help stratify care by both identifying patients unlikely to remit who may warrant earlier biologic therapy and avoid biologics in those likely to improve with standard treatment. This abstract is funded by: National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC)
Yang et al. (Fri,) studied this question.