Impact of severe exacerbations on lung function in dupilumab-treated patients: LIBERTY ASTHMA QUEST

Abstract

<b>Background:</b> Severe asthma exacerbations can rapidly impair lung function. Dupilumab (DPL), a fully human mAb, blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 (T2) inflammation. In phase 3 QUEST (NCT02414854), add-on DPL 200/300mg every 2 weeks vs placebo (PBO) reduced severe exacerbations and improved FEV₁ in patients (pts) with uncontrolled, moderate-to-severe asthma with ≥1 exacerbation prior to enrollment. DPL was generally well tolerated. Effects of DPL were greater in pts with elevated T2 biomarkers at baseline (BL). <b>Aim:</b> To assess the impact of severe exacerbations on post-bronchodilator (BD) FEV₁ in QUEST pts with T2 (≥150 eosinophils [eos]/µL and/or FeNO ≥25ppb) or T2-high asthma (≥300eos/µL and/or FeNO ≥25ppb) at BL. <b>Methods:</b> Change from BL in post-BD FEV₁ after the first severe exacerbation was assessed post hoc in DPL vs PBO pts censoring data at onset of potential second severe exacerbation. <b>Results:</b> Post-BD FEV₁ recovered faster after an exacerbation in pts on DPL vs PBO (<b>Figure</b>). Benefits were greater within 6 weeks of exacerbation and were sustained over time. Pts with T2-high asthma at BL benefited most from DPL. <b>Conclusion:</b> DPL vs PBO reduced impact of exacerbations on post-BD FEV₁ in pts with moderate-to-severe asthma and elevated T2 biomarkers at BL. Improvement was rapid and suggests a sustained response to DPL and lung function recovery after an exacerbation.