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INTRODUCTION:: Severe asthma imposes a substantial clinical, social, and economic burden, particularly within healthcare systems facing increasing pressure to ensure access to innovations such as biologics. Traditional economic evaluations, focused on single strategies, are often insufficient to capture the broader impact of integrated policy interventions. This study assesses the clinical, economic, social, and fiscal impact of three policy strategies for severe asthma management in Italy: (i) improved treatment adherence, (ii) expanded access to biologics, and (iii) earlier disease identification through structured healthcare approaches, using a multidimensional predictive modeling framework.

METHODS:: A combined methodological approach was adopted, integrating a Budget Impact Analysis, a cost-of-illness model, and a Markov model over a five-year horizon. The model was developed from the perspectives of the National Health Service, society, and the fiscal system. Clinical and economic inputs were derived from national tariffs, AIFA transparency lists, and the scientific literature.

RESULTS:: The baseline scenario shows increasing costs over five years, mainly driven by exacerbation management and productivity losses. Policy 1 and Policy 3 generate cost reductions compared with the baseline scenario, whereas Policy 2 increases expenditures due to higher biologic uptake. The integrated scenario yields an overall benefit, with a cumulative reduction of € 3.5 billion and improvements across all perspectives.

CONCLUSIONS:: Integrated care pathways combining early diagnosis, improved adherence, multidisciplinary management, and appropriate biologic use represent the most effective strategy to improve outcomes while maintaining sustainability. These findings highlight the need for systemic policies supporting equitable access to innovation.