1. What is already known about this topic?

A minority of patients with evidence of severe eosinophilic asthma do not respond adequately to eosinophil directed anti-IL5/5R therapies. In addition to targeting eosinophil chemotaxis, dupilumab targets other potentially relevant IL-13 pathways that may be clinically important in this subgroup. It is unclear whether a switch to dupilumab leads to improved clinical outcomes in this cohort.

2. What does this article add to our knowledge?

This is the first report of the extended 2-year response to dupilumab in patients with SEA failing to respond adequately to anti-IL5/5R therapies. We report clinically significant improvements in the majority of patients including the ability to achieve clinical remission in over 40%. A higher pre-biologic FeNO was observed in the patients achieving clinical remission with dupilumab following a failure of anti-IL5/5R therapies, pointing to an IL-13 dominant sub-phenotype of T2-high asthma in which targeting the eosinophil appears less clinically relevant.

3. How does this study impact current management guidelines?

This analysis highlights that many non-responders to anti-IL-5/5R treatment can go on to achieve clinical remission following a switch to dupilumab. Clinicians should be encouraged to assess FeNO when considering the likely benefit of switching from anti-IL5/5R therapies to dupilumab.