{
  "abstract": "Introduction and Objectives Spirometry-derived ratios can be used to distinguish restrictive and obstructive lung disease and guide treatment decisions in patients with asthma. Knowing their relationship with type 2 biomarkers and symptom control could help assess responses to biologic treatments. Dupilumab, a fully human monoclonal antibody that blocks signaling of interleukin (IL)-4 and IL-13, improves lung function in patients with type 2, moderate-to-severe asthma. Here, we assess the effect of dupilumab on large and small airway dysfunction using spirometry-derived ratios and whether changes correlate with changes in fractional exhaled nitric oxide (FeNO) and symptom control in patients with asthma.Methods In the phase 4 VESTIGE trial ( NCT04400318), adults (aged 21–70 years) with type 2 (eosinophils ≥300 cells/µL and FeNO ≥25 ppb), uncontrolled, moderate-to-severe asthma were randomized to receive add-on dupilumab 300 mg (n=72) or placebo (n=37) q2w for 24 weeks. Using a mixed model for repeated measures, we evaluated changes from baseline at Weeks 4, 12, and 24 in four spirometry ratios: absolute and percent predicted (pp) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) and forced mid-expiratory flow at 25% to 75% of pulmonary flow (FEF25–75%)/FVC, which assess large and small airway dysfunction, respectively. Using Pearson’s correlation coefficient (r), we assessed relationships between changes in each ratio at Week 24 and changes in FeNO level and 5-item Asthma Control Questionnaire (ACQ-5) score at Week 24.Results Mean baseline values for each spirometry-derived ratio were comparable for dupilumab and placebo ( table 1). Dupilumab vs placebo improved all ratios by Week 4 and through Week 24 (table 1). With dupilumab, at Week 24, change in all ratios inversely correlated with change in FeNO (FEV1/FVC: r=−0.31, P<0.01; ppFEV1/ppFVC: r=−0.31, P<0.01; FEF25–75%/FVC: r=−0.32, P<0.01; ppFEF25–75%/ppFVC: r=−0.33, P<0.01) and change in ACQ-5 scores (FEV1/FVC: r=−0.27, P<0.05; ppFEV1/ppFVC: r=−0.28, P<0.05; FEF25–75%/FVC: r=−0.24, P<0.05; ppFEF25–75%/ppFVC: r=−0.25, P<0.05). No significant correlations were observed in patients receiving placebo.Abstract P197 Table 1Change from baseline in spirometry-derived ratios over time in patients with type 2, moderate-to-severe asthma from VESTIGEConclusions In patients with type 2, moderate-to-severe asthma, dupilumab significantly increased spirometry-derived ratios, indicating improved large and small airway function. Increases in these ratios correlated with reductions in FeNO and improvements in asthma control.",
  "authors": [
    {
      "affiliations": [
        "University of Dundee, Dundee, UK"
      ],
      "name": "BJ Lipworth"
    },
    {
      "affiliations": [
        "University Hospital Essen – Ruhrlandklinik, Essen, Germany"
      ],
      "name": "C Taube"
    },
    {
      "affiliations": [
        "University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "P Rogliani"
    },
    {
      "affiliations": [
        "Shizuoka General Hospital, Shizuoka, Japan"
      ],
      "name": "T Shirai"
    },
    {
      "affiliations": [
        "West China Hospital, West China School of Medicine, Sichuan University, Chengdu, China"
      ],
      "name": "F Wen"
    },
    {
      "affiliations": [
        "Hospital Clínico Universitario de Santiago de Compostela-Grupo de Investigación TRIAD, Santiago de Compostela, Spain"
      ],
      "name": "FJ González-Barcala"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, MA, USA"
      ],
      "name": "A Altincatal"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA"
      ],
      "name": "R Gall"
    },
    {
      "affiliations": [
        "Sanofi, Cambridge, MA, USA"
      ],
      "name": "H Awad"
    },
    {
      "affiliations": [
        "University of Kansas School of Medicine, Kansas City, USA"
      ],
      "name": "M Castro"
    }
  ],
  "title": "P197 Dupilumab causes improvements in spirometry ratios in patients with moderate-to-severe asthma, which correlate with changes in fractional exhaled nitric oxide and asthma control",
  "uid": "56da813d-486d-5d56-91b3-41586a483626"
}