{
  "abstract": "Introduction and Objectives Cardiovascular disease (CVD) and metabolic disease (metD) are common comorbidities in chronic obstructive pulmonary disease (COPD) and may modulate clinical outcomes and therapy response. In BOREAS and NOTUS, add-on dupilumab reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation. Safety was consistent with the known dupilumab safety profile. This post hoc analysis assessed dupilumab efficacy in patients with COPD with/without CVD or metD.Methods BOREAS ( NCT03930732) and NOTUS (NCT04456673), phase 3 RCTs, enrolled patients (40– 85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on triple therapy. Patients received dupilumab 300 mg or placebo q2w for 52 weeks. Endpoints: annualized moderate or severe exacerbation rates, and change from baseline at Week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and St. George’s Respiratory Questionnaire (SGRQ) total scores (range: 0–100 points; lower scores indicating better quality of life) in the pooled intention-to-treat population with/without investigator-reported CVD or metD.Results Of 1,874 patients, 1,253 (66.9%) had a history of CVD and 758 (40.4%) of metD. Dupilumab reduced exacerbation rates by 31–33%, with relative risk vs placebo (95%CI) of 0.69 (0.59, 0.82; P<0.001) with CVD, 0.67 (0.51, 0.89; P=0.005) without CVD, and 0.68 (0.54, 0.85; P<0.001) with metD, 0.69 (0.57, 0.84; P<0.001) without metD. Dupilumab improved Week 52 pre-bronchodilator FEV1 across all subgroups by LS mean difference vs placebo (95%CI) of 55 mL (18, 92; P=0.004) with CVD, 104 mL (42, 166; P=0.001) without CVD, and 62 mL (12, 112; P=0.015) with metD, 77 mL (35, 119; P<0.001) without metD. Dupilumab also reduced Week 52 SGRQ total scores by LS mean difference vs placebo (95%CI) of −3.1 points (−4.9, −1.2; P=0.001) with CVD, −3.3 points (−6.1, −0.4; P=0.026) without CVD, and −2.5 points (−4.8, −0.1; P=0.040) with metD, −3.9 points (−6.0, −1.9; P<0.001) without metD. All interaction P values for data presented were >0.05.Conclusion Dupilumab reduced moderate or severe exacerbation rates, and improved lung function and quality of life in patients with COPD and type 2 inflammation, regardless of comorbid CVD or metD.",
  "authors": [
    {
      "affiliations": [
        "University College London, London, UK"
      ],
      "name": "JR Hurst"
    },
    {
      "affiliations": [
        "University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "P Rogliani"
    },
    {
      "affiliations": [
        "LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf, Germany"
      ],
      "name": "KF Rabe"
    },
    {
      "affiliations": [
        "University of British Columbia, Vancouver, BC, Canada"
      ],
      "name": "NM Hawkins"
    },
    {
      "affiliations": [
        "Johns Hopkins University School of Medicine, Baltimore, MD, USA"
      ],
      "name": "NN Hansel"
    },
    {
      "affiliations": [
        "University of Marburg, German Center for Lung Research (DZL), Marburg, Germany"
      ],
      "name": "CF Vogelmeier"
    },
    {
      "affiliations": [
        "University of Alabama at Birmingham, Birmingham, AL, USA"
      ],
      "name": "SP Bhatt"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA"
      ],
      "name": "C Xia"
    },
    {
      "affiliations": [
        "Sanofi, Morristown, NJ, USA"
      ],
      "name": "J Heble"
    },
    {
      "affiliations": [
        "Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA"
      ],
      "name": "M Soliman"
    }
  ],
  "title": "S101 Impact of dupilumab in patients with chronic obstructive pulmonary disease with cardiovascular or metabolic comorbidities: BOREAS and NOTUS trials",
  "uid": "ae6fc5e8-0605-58b9-8111-5e0ea269d996"
}