Analysis of trends in single inhaler triple therapy (SITT) use and clinical characteristics of patients with severe asthma: data from the IRSA registry.

Background. Triple therapy with inhaled corticosteroids (ICS), long-acting β₂-agonists (LABA), and long-acting muscarinic antagonists (LAMA) is recommended for severe asthma patients with uncontrolled symptoms. Single-inhaler triple therapy (SITT) may offer additional clinical and practical benefits. This study analyzes the clinical profiles of patients receiving LAMA-containing regimens using real-world data from the Italian Registry on Severe Asthma (IRSA). Methods. We conducted a cross-sectional analysis of 2,155 patients with severe asthma enrolled in IRSA between 2018 and May 2025. Patients were stratified based on LAMA use ("LAMA Yes" vs. "LAMA No") and assessed across demographics, lung function, biomarkers, asthma control, healthcare utilization, and comorbidities. Results. Patients on triple therapy were older, had a greater smoking history, and worse lung function (FEV₁ and FVC, p<0.001). They also reported poorer asthma control (mean ACT 16 vs. 17.5, p<0.001), more exacerbations (3.6 vs. 2.8/year, p<0.001), higher systemic corticosteroid use, and more comorbidities, including obesity and bronchiectasis. Interestingly, no significant differences were observed in type 2 inflammation markers (eosinophils, FeNO). The odds of receiving a LAMA prescription increased with age and a higher number of exacerbations. Conclusions. Triple therapy, especially through SITT, identifies a clinically complex asthma phenotype with a high disease burden. Despite growing evidence supporting efficacy and adherence benefits, triple therapy remains relatively underutilized in clinical practice, albeit with a significant increase from 2023 to the present. These findings highlight the need for more careful prescribing and further real-world evidence to optimize SITT positioning before escalation to biologic treatments.