Background Prior asthma exacerbations have been associated with lung function decline and increased risk of future exacerbations. Dupilumab (DPL) blocks IL-4/IL-13, key drivers of type 2 inflammation. In phase 3 QUEST (NCT02414854), add-on DPL significantly reduced severe exacerbations and improved lung function in patients (pts) with uncontrolled, moderate-to-severe asthma. TRAVERSE (NCT02134028), evaluated DPL long-term safety, tolerability, and efficacy in pts from a previous DPL asthma study. DPL safety profile during TRAVERSE was consistent with the known safety profile.
Aim To examine the relationship between prior exacerbations and lung function in pts with type 2 asthma (blood eosinophils≥150 cells/µL or FeNO≥25 ppb at parent study baseline [PSBL]) from QUEST enrolled in TRAVERSE.
Methods Pts on DPL in QUEST continued DPL 300 mg (DPL/DPL) in TRAVERSE for up to 96 weeks; pts on placebo in QUEST started DPL (PBO/DPL). Endpoints: annualized severe exacerbation rate (AER); change from baseline in pre-bronchodilator (pre-BD)% predicted (pp) FEV1 in non-exacerbators (0 exacerbations) and exacerbators (≥1 exacerbations) during QUEST.
Results In the exacerbator group, DPL vs placebo reduced AER in QUEST (1.67 vs 2.59, respectively) and TRAVERSE (DPL/DPL 0.78 and PBO/DPL 0.56). In the non-exacerbator group, DPL maintained low AER (0.11 DPL/DPL and 0.17 PBO/DPL) in TRAVERSE. Mean pre-BD ppFEV1 change from PSBL at Week 96 was 10.09 vs 14.84 percentage points for DPL/DPL vs PBO/DPL in the exacerbator group and 13.28 vs 13.10 percentage points in the non-exacerbator group.
Conclusions DPL’s dual mechanism of action via IL-4/IL-13 improved exacerbations and lung function in PBO/DPL subjects, and sustained improvement in DPL/DPL subjects irrespective of prior exacerbation status.
