Tezepelumab reduces mucus plugging in patients with moderate to severe uncontrolled asthma

Tezepelumab treatment reduced mucus scores, which correlated with lung function improvement, among patients with moderate to severe uncontrolled asthma, researchers reported at the European Respiratory Society International Congress.

“It’s the first time we’ve been able to demonstrate in a randomized controlled trial reduction of mucus plugging in response to a biologic therapy targeted extremely well vs. placebo,” Christopher E. Brightling, MD, PhD, National Institute for Health and Care Research (NIHR) senior investigator and clinical professor in respiratory medicine at the University of Leicester, U.K., said during a presentation.

Brightling presented results of an exploratory post hoc analysis of the phase 2, double-blind, placebo-controlled CASCADE study. Researchers randomly assigned 116 patients aged 18 to 75 years with moderate to severe uncontrolled asthma to treatment with subcutaneous tezepelumab-ekko 210 mg (Tezspire, Amgen/AstraZeneca) or placebo every 4 weeks for 28 weeks. A radiologist scored mucus plugging at baseline and at the end of the treatment period in 18 lung segments using CT imaging. Mucus plugs were defined as capacities that completely occluded the lumen of the segmental or subsegmental airway, Brightling said.

Baseline distribution of mucus scores was similar to that previously described in patients with severe asthma, Brightling said during the presentation.

At baseline, there was a positive correlation between patient mucus score and blood eosinophils, eosinophil-derived neurotoxin, fractional exhaled nitric oxide, interleukin (IL)-5 and IL-13. The researchers reported a negative correlation between patient mucus score and pre-bronchodilator FEV₁ and forced expiratory flow of 25% to 75%.

Compared with placebo, treatment with tezepelumab reduced mucus plugging scores; the mean change was –1.7 among 37 patients in the tezepelumab group and 0 among 45 patients in the placebo group (P = .0007).

The reduction in mucus plugging score correlated with improvements in lung function measured by pre-bronchodilator FEV₁ (P = .00014) and forced expiratory flow of 25% to 75% (P = .0006), Brightling said.