|May 20, 2019, 9:15 AM – 11:15 AM||Room D222-D224 (Level 2), KBHCCD|
- N. A. Hanania1, E. D. Bateman2, M. Castro3, I. D. Pavord4, A. Papi5, J. M. FitzGerald6, J. F. Maspero7, C. Katelaris8, D. Singh9, M. S. Rice10, P. Rowe11, Y. Lu12, N. Amin12, H. W. Staudinger11, N. M. H. Graham12, A. Teper11;
1Baylor College of Medicine, Houston, TX, United States, 2University of Cape Town, Cape Town, South Africa, 3Washington University School of Medicine, St. Louis, MO, United States, 4University of Oxford, Oxford, United Kingdom, 5University Hospital Santa Anna, Ferrara, Italy, 6University of British Columbia, Vancouver, BC, Canada, 7Fundación CIDEA, Buenos Aires, Argentina, 8Campbelltown Hospital and Western Sydney University, Sydney, Australia, 9University of Manchester, Manchester University Foundation Trust NHS Hospital, Manchester, United Kingdom, 10Sanofi, Cambridge, MA, United States, 11Sanofi, Bridgewater, NJ, United States, 12Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States.
- Rationale: Dupilumab, a fully human VelocImmune®-derived anti-interleukin (IL)-4 receptor α monoclonal antibody, inhibits signaling of IL-4 and IL-13, which are key drivers of type 2 inflammation. Dupilumab is approved for the treatment of inadequately controlled, moderate-to-severe atopic dermatitis and, in the USA, for patients aged ≥12 years with moderate-to-severe eosinophilic or corticosteroid-dependent asthma. In the phase 3 LIBERTY ASTHMA QUEST study (NCT02414854), add-on dupilumab 200mg and 300mg every 2 weeks (q2w), vs placebo, significantly reduced annualized severe exacerbation rates, improved pre-bronchodilator forced expiratory volume in 1 second (FEV1), and improved quality-of-life measures in the overall population of patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater with elevated type 2 biomarkers at baseline (blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide [FeNO] ≥25 ppb). This post hoc analysis assessed the efficacy of dupilumab in patients with late onset of asthma (age >40 years) and baseline post-bronchodilator FEV1/forced vital capacity [FVC] ratio <0.7 (which suggests fixed airway obstruction) or ≥0.7. Methods: Annualized rate of severe exacerbations during the 52-week treatment period was analyzed using negative binomial regression models. Change from baseline in pre- and post-bronchodilator FEV1 (L) and pre-bronchodilator FEV1/FVC ratio at Weeks 12 and 52 were analyzed using mixed-effect models with repeated measures. Results: Dupilumab 200mg and 300mg q2w vs placebo significantly reduced the annualized rate of severe exacerbations in patients with late-onset asthma and fixed airway obstruction (─68.8% and ─75.7%, respectively, both P<0.0001) and in patients without fixed airway obstruction (─55.1% and ─50.7%, respectively, both P<0.05) (Table). At Week 12, pre- and post-bronchodilator FEV1 and FEV1/FVC ratio improved in dupilumab-treated patients with late-onset asthma and fixed airway obstruction (P<0.05 vs placebo, either or both doses); similar improvements were observed at Week 52 (dupilumab 200mg q2w P<0.05 for pre- and post-bronchodilator FEV1; dupilumab 300mg q2w pre-bronchodilator FEV1 P=0.09, post-bronchodilator FEV1 P=0.06). Late-onset asthma patients without fixed airway obstruction had more modest improvements vs placebo in pre-bronchodilator FEV1 at Weeks 12 and 52 than did those with fixed airway obstruction (P≥0.05). The most frequent adverse event in dupilumab-treated groups vs matched-placebo was injection-site reactions (15%/18% vs 5%/10%, respectively). Conclusion: In patients with late-onset asthma with or without fixed airway obstruction, dupilumab significantly reduced severe exacerbation rates. Furthermore, lung function improvements were observed at Weeks 12 and 52 in patients with late-onset asthma and fixed airway obstruction, who typically experience worse asthma outcomes than do those without fixed airway obstruction.