Background: The definition of severe uncontrolled asthma and the best phenotype-driven management are not fully established.
Objective: We aimed to reach a consensus on the definition of severe uncontrolled asthma and give recommendations on optimal management with phenotype-targeted biological therapies.
Methods: A modified Delphi technique was used. A scientific committee provided statements addressing the definition of severe uncontrolled asthma and controversial issues about its treatment with biologics. The questionnaire was evaluated in 2 rounds by expert allergists. With the results, the scientific committee developed recommendations and a practical algorithm.
Results: A panel of 27 allergists reached agreement on 27 out of the 29 items provided (93.1%). A consensus definition of severe uncontrolled asthma was agreed. Prior to initiation of therapy, it is mandatory to establish the asthma phenotype and assess the presence of clinically important allergic sensitizations. Anti-IgE, anti–IL-5, anti–IL-5 receptor, and anti–IL-13/IL-4 receptor inhibitors are suitable options for patients with allergic asthma and a blood eosinophil level >300/μL (>150/μL in patients receiving oral corticosteroids). IL-5 and anti–IL-5 receptor inhibitors are recommended for patients with an eosinophilic phenotype and can also be used for patients with severe eosinophilic allergic asthma with no or a suboptimal response to omalizumab. Dupilumab is recommended for patients with moderate-severe asthma and a TH2-high phenotype. Only physicians with experience in the treatment of severe uncontrolled asthma should initiate biological treatment.
Conclusion: We provide consensus clinical recommendations that may be useful in the management of patients with severe uncontrolled asthma.

Key words: Asthma, Delphi technique, Consensus, Biological therapy, Monoclonal antibodies, Algorithms