Dupilumab improves exacerbations and lung function irrespective of prior asthma exacerbations: TRAVERSE

Abstract

<b>Background:</b> Prior asthma exacerbations have been associated with lung function decline/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/improved lung function in patients with uncontrolled, moderate-to-severe asthma. TRAVERSE (NCT02134028), evaluated DPL long-term safety, tolerability, and efficacy in patients from a previous DPL asthma study. <b>Aim:</b> To examine the relationship between prior exacerbations and lung function in T2 asthma patients (serum eos ≥150 cells/µL or FeNO ≥25 ppb at baseline) from QUEST enrolled in TRAVERSE. <b>Methods:</b> Patients on DPL in QUEST continued DPL 300mg (DPL/DPL) in TRAVERSE for up to 96 weeks; patients on placebo in QUEST started DPL (PBO/DPL). Endpoints: annualized severe exacerbation rate (AER); change from baseline in % predicted (pp) FEV1 in non-exacerbators (0 exacerbations) and exacerbators (≥1 exacerbations) during QUEST. <b>Results:</b> 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 pp FEV1 change at Week 96 was 10.09 vs 14.84 for DPL/DPL vs PBO/DPL in the exacerbator group; 13.28 vs 13.10 for DPL/DPL vs PBO/DPL in the non-exacerbator group. DPL safety during TRAVERSE was consistent with the known safety profile. <b>Conclusions:</b> 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.