Exacerbation Risk and Type 2 Inflammation in Placebo Patients During a Phase 2b Study of Dupilumab in Patients With Uncontrolled Persistent Asthma
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Mario Castro, MD, MPH, FCCP, Brian N. Swanson, PhD, Shyamalie Jayawardena, Jennifer D. Hamilton, PhD, Nikhil Amin, Gianluca Pirozzi, Neil M.H. Graham, Ariel Teper, MD

Therapies that inhibit type 2 inflammation have shown efficacy in the treatment of asthma, though the relative importance of underlying immunological mechanisms remains unclear. To understand the relationship between severe asthma exacerbation rates and type 2-related biomarkers, this post hoc analysis examines the placebo cohort in a pivotal phase 2b dupilumab asthma study (NCT01854047). Dupilumab is approved by the US FDA for treatment of adults with moderate-to-severe atopic dermatitis.


Adults with uncontrolled persistent asthma on medium-to-high-dose ICS+LABA were randomized to 24 weeks of add-on therapy with subcutaneous dupilumab or placebo. Observed annualized exacerbation rates in patients randomized to placebo (n=158) for 40 weeks (24 weeks treatment, 16 weeks follow-up) of observation period were examined by baseline lowest vs highest quartiles of fractional exhaled nitric oxide (FeNO; <16 vs ≥48 ppb), serum periostin (<67 vs ≥111 ng/mL), blood eosinophils (<0.15 vs ≥0.42 Giga/L), and IgE (<76 vs ≥436 kU/L) levels.


During the 40-week observation period, annualized exacerbation rates were numerically higher in patients with higher baseline biomarkers indicative of type 2 inflammation vs lower: FeNO (1.54 vs 0.98), periostin (1.42 vs 0.80), and eosinophils (1.31 vs 0.43). Higher (vs lower) baseline total IgE was less clearly associated with higher exacerbation rates (1.07 vs 0.94).


Patients in the highest quartiles for FeNO, periostin, and eosinophils experienced numerically higher exacerbation rates during 40 weeks of observation (interpretation was less clear for IgE). FeNO, periostin, and eosinophils may have potential value in identifying asthma patients at higher risk of severe asthma exacerbations.