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

The QUEST ( identifier ) and TRAVERSE () 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. This analysis assessed dupilumab efficacy in patients from QUEST who enrolled in TRAVERSE and were stratified by a reduction in fractional exhaled nitric oxide (F) level by week 2 of QUEST. Patients with an F level of at least 25 ppb at parent study baseline (PSBL) were defined as those with or without a minimally important F level reduction/response (a ≥20% reduction in patients with an F level of ≥50 ppb and a reduction of >10 ppb in those with an F 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 value, 5-item Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score. During QUEST, dupilumab (compared with placebo) reduced AER by 58% to 59% across F response subgroups (unadjusted AER = 0.392-0.523 for dupilumab vs 1.052-1.280 for placebo) and improved prebronchodilator FEV value regardless of F response. These improvements were sustained during TRAVERSE, with a slightly greater magnitude in F responders. Dupilumab also improved 5-item Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores independently of F responses. Dupilumab sustained efficacy for up to 3 years in patients with and without a minimally important early reduction in F level. Greater improvements were seen in patients with an early reduction in F level, but patients without such a reduction also showed favorable outcomes during their treatment with dupilumab.