{
  "abstract": "Introduction Tezepelumab is an anti-TSLP biologic therapy with broad anti-inflammatory effects. Clinical trials have been demonstrated its ability to significantly reduce asthma exacerbations (AE) and allow clinical remission (CR) in some patients with uncontrolled, severe asthma (SA). However, a proportion of patients do not adequately respond and continue to exacerbate on tezepelumab. The clinical characteristics of these ‘non-responders’ is poorly understood.Methods The clinical response of individuals with SA established on treatment with tezepelumab at our regional severe asthma centre was analysed. The baseline characteristics of patients who achieved CR (defined as no AE, no maintenance OCS, ACQ6<1.5 and stable FEV1) was compared with non-responders (NR) defined as ≥2 exacerbations in the first year of tezepelumab.Results Out of a total cohort of 218 patients, 103 patients had either achieved CR (n=54, 25%) or fulfilled criteria for NR (n=49, 22%) and were compared. Baseline clinical characteristics associated with NR vs CR included lower FeNO (35ppb vs 66ppb, p<0.001), higher baseline ACQ6 (2.90 vs 1.95, p<0.001), maintenance OCS requirement (p=0.03), higher baseline AE rate (3.6 vs 2.3, p=0.009), child-onset asthma (p=0.01) and the absence of comorbid nasal polyposis (p=0.006). The reduction in FeNO from baseline to treatment was significantly greater in patients achieving CR compared to NR, with median (IQR) changes of -43 ppb (-70 to -13) versus -4 ppb (-25 to 3), respectively ( p<0.0001).Conclusion Over 20% of individuals with SA continue to exacerbate frequently despite tezepelumab. Reduced efficacy in patients with lower baseline FeNO, child-onset asthma and the absence of nasal polyposis all point to an increased likelihood of non-T2 related exacerbation events in these patients.",
  "authors": [
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK",
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "F Haris"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK",
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "J Gates"
    },
    {
      "affiliations": [
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "F Cefaloni"
    },
    {
      "affiliations": [
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "P Khooshemehri"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "L Green"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "M Fernandes"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "L Thomson"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "C Roxas"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "J Lam"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "G d’Ancona"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK",
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "AM Nanzer"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK"
      ],
      "name": "J Dhariwal"
    },
    {
      "affiliations": [
        "Guy’s Severe Asthma Centre, Guy’s and St Thomas’ NHS Trust, London, UK",
        "School of Immunology and Microbial Sciences, King’s College London, London, UK"
      ],
      "name": "DJ Jackson"
    }
  ],
  "title": "P195 Phenotypic characteristics associated with frequent asthma exacerbations on tezepelumab",
  "uid": "81f27888-46cc-56f5-a4ef-685829737aa6"
}