Effect of dupilumab on severe exacerbations in asthma patients with and without lung function improvements

Background: Dupilumab (DPL), a fully human mAb, blocks the shared receptor component of IL-4/IL-13, key and central drivers of type 2 inflammation. In phase 3 QUEST (NCT02414854), DPL 200/300mg every 2 weeks vs placebo (PBO) reduced severe asthma exacerbations and improved pre-bronchodilator (BD) FEV1 in patients (pts) with uncontrolled, moderate-to-severe asthma. Aim: To assess DPL efficacy in reducing severe asthma exacerbations in pts from QUEST overall ITT with and without clinically meaningful improvements (≥100 or ≥200mL) in pre-BD FEV1 at Week (Wk) 12. Methods: Annualized severe exacerbation event rate during the 52-week treatment period was assessed. Results: Of 1,902 pts (1,264 DPL/638 PBO), more DPL- vs PBO-treated pts had pre-BD FEV1 improvements of ≥100mL (780 [62%] vs 315 [49%]) and ≥200mL (619 [49%] vs 237 [37%]) at Wk 12. DPL 200/300mg vs PBO significantly (P Conclusions: More DPL- vs PBO-treated pts with moderate-to-severe asthma had clinically meaningful pre-BD FEV1 improvements of ≥100 or ≥200mL at Wk 12. During the 52-week treatment period, DPL significantly reduced severe exacerbations vs PBO regardless of pre-BD FEV1 improvement at Wk 12.