{
  "abstract": "Introduction and Objectives Dupilumab, a human monoclonal antibody, blocks interleukin-4/13 signalling, key and central drivers of type 2 inflammation. In BOREAS and NOTUS, dupilumab reduced exacerbations and improved lung function in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. This post hoc analysis assessed whether early lung function improvement correlates with reduction in moderate exacerbations and symptom burden, and improved quality of life over 52 weeks in patients from BOREAS and NOTUS.Methods BOREAS ( NCT03930732) and NOTUS (NCT04456673), phase 3 randomized, double-blind, placebo-controlled trials, enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on triple therapy. Patients received add-on subcutaneous dupilumab 300 mg or matching placebo q2w for 52 weeks. Endpoints were change in annualized moderate or severe COPD exacerbation rates, comparing patients with Week 4 change from baseline in post-bronchodilator forced expiratory volume in 1 second (FEV1) of <150 mL vs ≥150 mL (threshold identifying patients with above average FEV1 improvement in the ITT population), as well as Pearson correlation coefficient (r) for Week 4 change of post-bronchodilator percent predicted (pp)FEV1 and Week 52 clinical outcomes: moderate or severe exacerbation rate, St. George’s Respiratory Questionnaire (SGRQ), and Evaluating Respiratory Symptoms in COPD (E-RS:COPD).Results In dupilumab recipients, moderate or severe exacerbations were reduced by 22% (relative risk: 0.78 [95% CI: 0.61, 0.98]; P=0.032) in those with improvement of post-bronchodilator FEV1 ≥150 mL at Week 4 compared with patients with <150 mL improvement. In patients receiving dupilumab, Week 4 change from baseline in post-bronchodilator ppFEV1 also correlated with a reduction in moderate exacerbation rates (r=–0.1043; P=0.0017), and Week 52 improvement in SGRQ (r=–0.2201; P<0.0001), and E-RS:COPD total scores (r=–0.1543; P<0.0001); the placebo arm did not show significant correlations, except with Week 52 SGRQ total scores (r=−0.1405, P=0.0002).Conclusion Patients with greater early lung function improvement had significantly greater reduction in moderate exacerbation. Early improvements in lung function were weak but significantly correlated with reductions in exacerbations and symptom burden at Week 52, as well as with improvements in quality of life.",
  "authors": [
    {
      "affiliations": [
        "Maastricht University Medical Center, Maastricht, Netherlands"
      ],
      "name": "FME Franssen"
    },
    {
      "affiliations": [
        "Baylor College of Medicine, Houston, TX, USA"
      ],
      "name": "NA Hanania"
    },
    {
      "affiliations": [
        "Hôpital Cochin AP-HP. Centre, Université Paris Cité, Paris, France"
      ],
      "name": "N Roche"
    },
    {
      "affiliations": [
        "Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China"
      ],
      "name": "R Chen"
    },
    {
      "affiliations": [
        "University of Michigan, Ann Arbor, MI, USA"
      ],
      "name": "WW Labaki"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "NN Hansel"
    },
    {
      "affiliations": [
        "Inserm U1250 U903, University Hospital of Reims, Reims, France"
      ],
      "name": "G Deslée"
    },
    {
      "affiliations": [
        "Sanofi, Reading, UK"
      ],
      "name": "R Wysoczanski"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA"
      ],
      "name": "C Xia"
    },
    {
      "affiliations": [
        "Sanofi, Morristown, NJ, USA"
      ],
      "name": "B Ferey"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA"
      ],
      "name": "M Soliman"
    }
  ],
  "title": "M14 Association between early lung function improvement with dupilumab and sustained clinical outcomes in patients with chronic obstructive pulmonary disease: a clinical perspective",
  "uid": "a38c3c41-c4b5-5fbe-86e3-c5f78479b77f"
}