Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma

Background: Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV₁) in patients with moderate-to-severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854). Methods: Changes from baseline in pre- and post-bronchodilator (BD) FEV₁ and 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2–150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb; type 2–300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non-exacerbators. Results: In exacerbators and non-exacerbators, dupilumab increased pre-BD FEV₁ by Week 2 vs placebo; differences were maintained to Week 52 (type 2–150/25: LS mean difference (LSMD) vs placebo: 0.17 L (95% CI: 0.10–0.24) and 0.17 L (0.12–0.23); type 2–300/25: 0.22 L (0.13–0.30) and 0.21 L (0.15–0.28)), in exacerbators and non-exacerbators, respectively (p <.0001). Similar trends were seen for post-BD FEV₁. Dupilumab vs placebo also showed significantly greater improvements in post-BD FEV₁ 0–42 days after first severe exacerbation in type 2–150/25 (LSMD vs placebo: 0.13 L [0.06–0.20]; p =.006) and type 2–300/25 (0.14 L [0.06–0.22]; p =.001) patients. ACQ-5 improvements were greater with dupilumab vs placebo in both groups. Conclusion: Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study.