Beyond Biologics: Background Inhaled Therapy Shapes Remission in Severe Asthma

BACKGROUND: Clinical remission has emerged as an achievable therapeutic goal in severe asthma treated with biologics. However, the potential influence of background inhaled therapy on remission outcomes remains insufficiently explored. This study evaluated whether baseline inhaled therapy, particularly extrafine single-inhaler triple therapy (SITT), influences the achievement of complete clinical remission in patients with severe asthma initiating biologic treatment. METHODS: We conducted a single-center retrospective observational study including adult patients with severe asthma who initiated biological therapy according to Italian regulatory criteria (AIFA). Baseline (T0) corresponded to the start of biologic therapy without modification of inhaled treatment. Inhaled therapy was maintained unchanged during the 12-month follow-up. All patients underwent a clinical reassessment at 3 months to evaluate asthma control, adherence, and exacerbation occurrence. Complete remission at 12 months was defined according to Severe Asthma Network Italy (SANI) criteria: absence of exacerbations, well-controlled symptoms (ACT ≥20), no oral corticosteroid use, stable lung function, and no change in inhaled therapy. Clinical, functional, and inflammatory variables were compared between patients achieving complete remission and those who did not. RESULTS: Twenty-nine patients were included (median age 53 years, IQR 41-59; 55.2% male). At baseline, inhaled therapy consisted of high-dose ICS/LABA in 37.9%, open triple therapy in 27.6%, and extrafine SITT in 34.5% of patients. At the 3-month reassessment, no patient experienced exacerbations or worsening of asthma control, and inhaled therapy was not modified. After 12 months of biologic therapy, 14 patients (48.3%) achieved complete clinical remission. Remission rates differed significantly according to inhaled therapy regimen (p = 0.001). The highest remission proportion was observed in patients receiving extrafine SITT (64.3%), followed by open triple therapy (21.4%) and high-dose ICS/LABA (14.3%). Patients achieving remission were significantly more likely to be receiving extrafine SITT at baseline (64.3% vs 6.7%), whereas high-dose ICS/LABA predominated among non-remission patients (60.0% vs 14.3%). No significant differences were observed between groups in demographic characteristics, asthma duration, lung function, inflammatory biomarkers (FeNO, eosinophils, IgE), comorbidities, or type of biologic therapy. CONCLUSIONS: In patients with severe asthma initiating biologic therapy, baseline inhaled therapy-particularly extrafine single-inhaler triple therapy- was associated with a higher likelihood of achieving complete clinical remission. The higher remission rate observed with extrafine SITT compared with open triple therapy or ICS/LABA is consistent with a potential synergistic interaction between optimized inhaled therapy targeting small airway dysfunction and biologic therapy targeting type-2 inflammation. These findings support the importance of maintaining optimized background inhaled therapy within a remission-driven treatment strategy. Prospective studies are warranted to confirm these observations.