Impact of early transient increase in eosinophils in patients with moderate-to-severe asthma on the long-term efficacy of dupilumab in TRAVERSE

<bold>Background:</bold> Some dupilumab-treated patients with moderate-to severe asthma experience early and usually transient increases in blood eosinophils (Eos). The QUEST (<ext-link>NCT02414854</ext-link>) and TRAVERSE (<ext-link>NCT02134028</ext-link>) studies have shown that dupilumab improves lung function in patients up to 148 weeks. This post hoc analysis evaluated the association between early, transient increases in Eos and long-term treatment outcomes. <bold>Methods:</bold> Patients from QUEST enrolled in TRAVERSE were stratified by ≥2-fold or <2-fold increase in Eos at QUEST Week 4. Changes from parent study baseline (PSBL) in unadjusted annualized severe asthma exacerbation rates (AER) and pre-bronchodilator (pre-BD) percent predicted forced expiratory volume in 1 second (ppFEV₁) at QUEST Week 52 and TRAVERSE Week 96 were assessed. <bold>Results:</bold> At QUEST Week 52, dupilumab treatment reduced AER in patients with ≥2-fold increase in Eos vs placebo (0.64 vs 1.19) and with <2-fold increase (0.47 vs 1.03). The LS mean difference [95%CI] from PSBL in pre-BD ppFEV₁ was significantly higher vs placebo at QUEST Week 52 in dupilumab-treated patients regardless of change in Eos (≥2-fold increase: 7.5[3.4–11.7]%; <2-fold increase: 5.3[3.8–6.8]%); both <italic>P</italic>>0.001. At TRAVERSE Week 96, AER was reduced and pre-BD ppFEV₁ improved in the placebo/dupilumab group while improvements were maintained in the dupilumab/dupilumab group. <bold>Conclusion:</bold> Dupilumab vs placebo reduced AER for up to 148 weeks regardless of any transient increase in Eos at Week 4 of QUEST, while dupilumab-treated patients who experienced ≥2-fold increase in blood Eos had statistically greater improvements in pre-BD ppFEV₁ than patients who did not.