How I do it. Choosing the right biologic for the right patient with severe asthma.

In this new instalment of the How I Do It: Severe Asthma series, we tackle the clinical conundrum of choosing the right biologic for the right patient with severe asthma. With 6 biologics now approved for use in this area comprising 4 different targeting strategies (anti-immunoglobulin E, omalizumab; anti-interleukin (IL)-5/5receptor, mepolizumab, reslizumab, and benralizumab; anti-IL-4receptor, dupilumab; anti-thymic stromal lymphopoietin, tezepelumab), this question is increasingly complex. Recognising that there is no head-to-head trial comparing biologics, we base our review on the expected effects of inhibiting different aspects of type-2 airway inflammation, supported whenever possible by clinical trial and real-world data. We use four variations of a case of severe uncontrolled asthma to develop concepts and considerations introduced in the previous Work-up of severe asthma installment and discuss pregnancy-, biomarker-, comorbidity-, and corticosteroid-dependency-related considerations when choosing a biologic. The related questions of deciding when, why, and how to switch from one biologic to another are also discussed. Overall, we consider that the choice between biologics should be based on the available clinical trial data for the desired efficacy outcomes; the biomarker profile of the patient; safety profiles (e.g., when pregnancy is considered); and opportunities to target two comorbidities with one biologic. Using systemic and airway biomarkers (blood eosinophils and exhaled nitric oxide (FeNO)) and other phenotypic characteristics, we suggest a framework to facilitate therapeutic decision-making. Post hoc studies and new comparative studies are urgently needed to test this framework and determine whether it allows us to make other clinically useful predictions.