Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study

Abstract

Theresa W Guilbert,1 Kevin R Murphy,2 Eckard Hamelmann,3 Kristie R Ross,4 Atul Gupta,5 Alessandro Fiocchi,6 Changming Xia,7 Rebecca Gall,7 Olivier Ledanois,8 Amr Radwan,7 Juby A Jacob-Nara,9 Paul J Rowe,9 Yamo Deniz7 1Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA; 2Boys Town National Research Hospital, Omaha, NE, USA; 3Department of Pediatrics, Children’s Center Bethel, University of Bielefeld, Bielefeld, Germany; 4UH Rainbow Babies and Children’s Hospital, Cleveland, OH, USA; 5King’s College Hospital, London, UK; 6Bambino Gesù Children’s Hospital IRCCS, Rome, Italy; 7Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 8Sanofi, Paris, France; 9Sanofi, Bridgewater, NJ, USACorrespondence: Theresa W Guilbert, Cincinnati Children’s Hospital and University of Cincinnati, Cincinnati, OH, USA, Tel [phone], Email [email protected]: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab.Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥ 5% or ≥ 10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12– 52, and mean change from baseline in ppFEV1 to Week 12.Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥ 5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥ 10%. During the Week 12– 52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52– 60% (all P< 0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥ 5%.Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12.Trial Registration: NCT02948959.Keywords: asthma, children, dupilumab, exacerbations, lung function, moderate-to-severe asthma, percent-predicted FEV1, uncontrolled asthma

Keywords

• asthma
• children
• dupilumab
• exacerbations
• lung function
• moderate-to-severe asthma
• percent-predicted fev1
• uncontrolled asthma