Dupilumab efficacy in patients with type 2 asthma and early FENO level reductions

Background: The QUEST (ClinicalTrials.gov identifier NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab, 200 or 300 mg, versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab, 300 mg, for an additional 96 weeks (TRAVERSE) in patients with uncontrolled, moderate-to-severe asthma. Objective: This analysis assessed dupilumab efficacy in patients from QUEST who enrolled in TRAVERSE and were stratified by a reduction in fractional exhaled nitric oxide (FENO) level by week 2 of QUEST. Methods: Patients with an FENO level of at least 25 ppb at parent study baseline (PSBL) were defined as those with or without a minimally important FENO level reduction/response (a ≥20% reduction in patients with an FENO level of ≥50 ppb and a reduction of >10 ppb in those with an FENO level of <50 ppb at PSBL) by week 2 of QUEST. We assessed annualized severe exacerbation rates (AERs) and changes from PSBL in prebronchodilator FEV ₁ value, 5-item Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score. Results: During QUEST, dupilumab (compared with placebo) reduced AER by 58% to 59% across FENO response subgroups (unadjusted AER = 0.392-0.523 for dupilumab vs 1.052-1.280 for placebo) and improved prebronchodilator FEV ₁ value regardless of FENO response. These improvements were sustained during TRAVERSE, with a slightly greater magnitude in FENO responders. Dupilumab also improved 5-item Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores independently of FENO responses. Conclusion: Dupilumab sustained efficacy for up to 3 years in patients with and without a minimally important early reduction in FENO level. Greater improvements were seen in patients with an early reduction in FENO level, but patients without such a reduction also showed favorable outcomes during their treatment with dupilumab.