Supplementary Material for: Biologic Therapy Timing and Severe Asthma Progression: Insights from the Italian Registry on Severe Asthma

Introduction: Timely initiation of biologic therapies is crucial in the management of severe asthma. However, delays in diagnosis and access to advanced treatments are common in real-life settings. We investigated disease progression and trajectories, with a focus on the impact of treatment latency among patients with severe asthma.
Methods: This longitudinal observational analysis included adult patients with severe asthma enrolled in the Italian Registry on Severe Asthma (IRSA). Data were stratified by use and timing of biologic therapy. Two core analyses were conducted: (1) characterization of patients not receiving biologics; (2) evaluation of disease progression and the relationship with the timing of biologic initiation.
Results: At baseline, 43.7% of the 2,114 patients were not receiving biologics, despite having severe disease and a T2-high phenotype. The average time of progression from initial diagnosis to severe asthma was 17 years. The median time from severe asthma diagnosis to biologic initiation was 2 years (IQR: 0.9–4.2). At the 1-year follow-up, patients who initiated biologics after enrollment showed the most significant clinical improvements compared with patients without biologic treatment or already on biologics at baseline, including a 64.8% reduction in the number of exacerbations (p=0.019), a mean reduction in annual exacerbation rate of 4.1 events (p<0.001), and an increase of 6.3 points in ACT score (p<0.001).
Conclusion: Severe asthma often develops after a prolonged progression from initial symptom onset. Structured referral and earlier biologic initiation may be associated with better outcomes and potentially influence the clinical trajectory of severe asthma.