Therapeutic Simplification in COPD and Its Impact on RADAR Control: Treatment-Burden Reduction, Responder Profile and Structural–Behavioral Trajectories

Background: Although single-inhaler triple therapy (SITT) improves COPD control, the specific structural and behavioral predictors of short-term clinical response following therapeutic simplification remain incompletely characterized. Methods: This prospective, multicenter observational study (N = 684) evaluated patients switching from triple therapy regimens involving multiple inhalers to SITT. A clinically meaningful response was defined as an intra-individual reduction of ≥2 points in the validated RADAR score at three months. Results: Therapeutic simplification reduced regimens requiring ≥4 inhalations/day from 46.1% to 14.3%, and poor behavioral adherence from 45.2% to 16.6%. Multivariable models identified an observed responder profile: higher baseline RADAR burden was the strongest predictor of improvement (aOR 2.00), whereas severe airflow limitation (FEV1 < 50%) attenuated the response. Exploratory mediation analysis indicated that 88.6% of the observed clinical stabilization was not explained by measured adherence changes, and may therefore also encompass unmeasured behavioral, educational or device-related factors. Patients burdened with both high complexity and poor adherence showed the highest rate of combined structural–behavioral improvement (25.0% vs. 4.7% overall). Conclusions: Switching from MITT to SITT was associated with reduced treatment complexity, improved adherence profiles, and short-term improvement in RADAR-defined clinical control. Patients with greater baseline RADAR burden and regimen complexity showed larger observed improvements.