Benralizumab treatment and SARP cluster analysis

Background: Severe asthma is heterogeneous, with different phenotypes and endotypes. Aims and Objectives: We identified subsets of benralizumab-treated patients (pts) with severe asthma by assignment to Severe Asthma Research Program (SARP) clinical clusters. Methods: Pts (N=2,281) from SIROCCO (Lancet 2016:2115; n=1,082) and CALIMA (Lancet 2016:2128; n=1,199) were assigned to clusters via a discriminant function based on 11 predictors. Drug responses were compared with the Kruskal-Wallis test (nominal p-values). Results: Pts met criteria for 4 of 5 SARP clusters. Cluster 2 pts (n=393) were 81% atopic with early onset moderate asthma (mean age 15 yrs). Cluster 4 pts (n=386) were 82% atopic with early onset severe asthma (mean age 11 yrs). Cluster 3 pts (n=641) were 50% atopic with late-onset severe asthma (mean age 47 yrs). Cluster 5 pts (n=861) were 55% atopic with late-onset asthma (mean age 33 yrs) and persistent airflow obstruction. All clusters had annual exacerbation rate reductions for combined benralizumab arms vs. placebo, which were greater in late-onset asthma clusters (Cluster 3, −48%; 5, −50%; p Conclusions: Benralizumab improved lung function and reduced exacerbations in all clusters, with greater effects in late-onset asthma Clusters 3 and 5 vs. early onset Clusters 2 and 4. This supports the importance of understanding asthma heterogeneity and responsiveness to targeted therapies.