BackgroundTransient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.ObjectiveWe assessed the effect of early increases in BEC on long-term treatment outcomes.MethodsPatients aged ≥12 years with moderate-to-severe type 2 asthma from the phase 3 QUEST study (NCT02414854; 52 weeks) who enrolled onto the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with or without ≥2-fold BEC increase any time by week 12 of QUEST, or presence or absence of increased BEC any time during QUEST (defined as <500 cells/μL at baseline but ≥500 cells/μL at any time during QUEST). End points included annualized severe exacerbation rate and change from parent study baseline in prebronchodilator forced expiratory volume in 1 second (FEV1), 5-item Asthma Control Questionnaire, and type 2 inflammatory biomarkers.ResultsA total of 36.6% of dupilumab-treated patients versus 21.7% of placebo-receiving patients experienced a ≥2-fold BEC change by week 12, while 31.3% versus 28.0% experienced increased BEC any time during QUEST. Dupilumab versus placebo reduced annualized severe exacerbation rate, improved prebronchodilator FEV1 and questionnaire scores, and reduced biomarkers across subgroups at week 52 of QUEST. Improvements were maintained in all subgroups through week 96 of TRAVERSE.ConclusionsDupilumab reduced asthma exacerbations and improved lung function and asthma control up to 148 weeks in patients with uncontrolled moderate-to-severe type 2 asthma irrespective of early transient increases in BEC. Overall safety was consistent with the known dupilumab safety profile.