Exacerbation trajectories in biologic-eligible severe asthma patients.

Abstract

Background: Asthma biologics are highly effective in reducing exacerbations. Improvement in exacerbations after biologic initiation is often attributed to treatment effect.

Research question: What proportion of biologic-eligible severe asthma patients improve without biologic therapy, and what characterises those who remain frequent exacerbators?

Study design and methods: Biologic-naïve adults with severe asthma were identified in nationwide UK electronic medical records. Year 0 was defined as the first year patients met severe asthma criteria with ≥3 systemic corticosteroid-treated exacerbations (biologic-eligible). Post-eligibility exacerbation trajectories were identified using longitudinal k-means. Sensitivity analyses included alternative k and a lower exacerbation threshold (≥2/year). Covariates included the highest blood eosinophil count, inhaled corticosteroid (ICS) dose and comorbidities.

Results: Among 10,078 biologic-eligible adults (median age 51 years; 71% female), we identified three exacerbation trajectories: (1) Remitting-stable (70%, n=7,091), with sustained improvement to <3 exacerbations/year even though ICS reduced after peak exacerbation year; (2) Chronic-frequent (20%, n=1,969), with persistently frequent exacerbations (median 5/year); (3) Refractory-frequent (10%, n=1,018), with high ongoing oral corticosteroid exposure (median >10 courses/year). Results were consistent across sensitivity analyses. Remitting-stable patients were least likely to have bronchiectasis but were otherwise similar in demographics and allergic comorbidities. Blood eosinophil count was higher in the chronic-frequent group (Year 0 median 0.30×10⁹/L) compared with remitting-stable (0.23×10⁹/L) and refractory-frequent groups (0.21×10⁹/L, p<0.001); this was evident several years before meeting biologic exacerbation criteria.

Interpretation: Over two-thirds of biologic-eligible patients improved with standard care alone. Chronic-frequent exacerbators had higher blood eosinophil counts, even years before meeting biologic criteria, suggesting a distinct disease phenotype.