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‘Fight club’ – Biologics in asthma: RCTs
S46 Tezepelumab reduces mucus plugging in patients with uncontrolled, moderate-to-severe asthma: the phase 2 CASCADE study
  1. L Nordenmark1,
  2. C Emson2,
  3. Å Hellqvist3,
  4. J Johnston4,
  5. H Greberg5,
  6. JM Griffiths2,
  7. JD Newell6,7,
  8. JR Parnes8,
  9. G Colice9,
  10. CE Brightling10
  1. 1Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R & D, AstraZeneca, Oslo, Norway
  2. 2Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R & D, AstraZeneca, Gaithersburg, Maryland, USA
  3. 3Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R & D, AstraZeneca, Gothenburg, Sweden
  4. 4Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R & D, AstraZeneca, Cambridge, UK
  5. 5Artificial Intelligence and Analytics, Data Science and Artificial Intelligence, R & D, AstraZeneca, Gothenburg, Sweden
  6. 6Department of Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA
  7. 7Medical Advisor to VIDA, Coralville, Iowa, USA
  8. 8Early Development, Amgen, Thousand Oaks, California, USA
  9. 9Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R & D, AstraZeneca, Gaithersburg, Maryland, USA
  10. 10Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK

Abstract

Background Mucus plugs are associated with airway inflammation and obstruction in patients with asthma. The impact of treatment on mucus plugs has not been investigated in randomized controlled trials (RCTs) of severe asthma.

Objective To assess mucus plugging in the lungs of patients with uncontrolled, moderate-to-severe asthma pre- and post-treatment with tezepelumab, a human monoclonal antibody that blocks thymic stromal lymphopoietin.

Methods CASCADE (NCT03688074) was an exploratory, double-blind, placebo-controlled study. Patients (18–75 years old) were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for at least 28 weeks. Mucus plugging was scored at baseline and end of treatment in 18 lung segments using standardized computed tomography imaging.

Results Mucus plugging scores were reduced in patients receiving tezepelumab (n = 37) versus placebo (n = 45) (nominal p = 0.0007; figure 1). At baseline, mucus score correlated positively with inflammatory markers (blood eosinophils, eosinophil-derived neurotoxin, fractional exhaled nitric oxide, IL-5 and IL-13) and negatively with lung function (FEV1 and FEF25–75%). Reduction in mucus score with tezepelumab was correlated with improvements in these lung function parameters.

Abstract S46 Figure 1
Abstract S46 Figure 1

Change in mucus plugging scores from baseline to EOT in patients receiving (A) tezepelumab 210 mg Q4W and (B) placebo

Conclusion Tezepelumab is the first biologic shown to reduce mucus plugging in patients with moderate-to-severe, uncontrolled asthma in an RCT.

Please refer to page A209 for declarations of interest related to this abstract.

https://doi.org/10.1136/thorax-2022-BTSabstracts.52

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