Tezepelumab in asthma: mucus plugging down, lung function up

Tezepelumab reduced mucus plugging in patients with moderate-to-severe asthma. Moreover, reductions in mucus scores correlated with improvements in lung function. Tezepelumab is the first biologic agent to demonstrate these results in a randomised-controlled trial, emphasised the authors of the study.

Mucus plugging is a common disease characteristic in patients with asthma and is associated with eosinophilic airway inflammation and airway obstruction [1]. “However, the effect of biologic treatment on mucus plugs in patients with severe asthma had not been assessed until the execution of the phase 2 CASCADE study (NCT03688074),” said Prof. Christopher Brightling (University of Leicester, UK). This trial randomised 116 patients with uncontrolled, moderate-to-severe asthma 1:1 to tezepelumab or placebo. The primary analysis of CASCADE demonstrated a reduced submucosal eosinophil count for patients receiving tezepelumab compared with those receiving placebo [2]. The current, exploratory, post-hoc analysis examined mucus plugging before and after treatment using CT imaging [3]. In total, 82 patients had CT scans at baseline and at the end of treatment.

Baseline mucus scores were similar to those of comparable populations in previously published studies [1]. At baseline, blood eosinophil count was positively correlated with mucus score (ρ=0.24; nominal P=0.0006). In addition, pre-bronchodilator forced expiratory volume in 1 second (FEV₁) scores were negatively related with mucus score (ρ=-0.325; nominal P=0.0017). After treatment, mucus scores were reduced in participants receiving tezepelumab but not in participants receiving placebo (mean change -1.7 vs 0.0; P=0.0007). Interestingly, post-treatment reductions in mucus scores correlated with improvements in lung function: change in pre-bronchodilator FEV₁ (ρ=-0.505; nominal P=0.00014; see Figure) and pre-bronchodilator forced expiratory flow (FEF) at 25–75% (ρ=-0.535; nominal P=0.0006).

Figure: Change from baseline in lung function parameters correlates with change from baseline in mucus score [3]



“This is the first, randomised-controlled trial to demonstrate the beneficial effect of a biologic agent on mucus plugging in patients with uncontrolled, moderate-to-severe asthma,” concluded Prof. Brightling.

1. Dunican EM, et al. J Clin Invest. 2018;128(3):997–1009.
2. Diver S, et al. Lancet Respir Med. 2021;9:1299–1312.
3. Nordenmark L, et al. Tezepelumab reduces mucus plugging in patients with uncontrolled, moderate-to-severe asthma: the phase 2 CASCADE studyALERT 4, RCT4445, ERS International Congress 2022, Barcelona, Spain, 4–6 September.

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Posted on 30 October, 2022